Blueprint Ingredients Review

Written by: Bryan Johnson
Published on: November 4, 2024
Blueprint Ingredients Review

Blueprint Ingredients Review

Written by: Bryan Johnson
Published on: November 4, 2024

What we put into our bodies matters. This review explores the ingredients in Blueprint products, highlighting their benefits, origins, and how they synergistically work to enhance your well-being. Whether you're a seasoned user or new to our offerings, this analysis will provide insight into how we developed the Blueprint program.

Summary:

Mitochondrial Support and Energy Production:

Supporting mitochondria health and energy production is fundamental to overall vitality, and certain ingredients play a crucial role in maintaining these processes. As we age, mitochondrial function declines, leading to fatigue, oxidative stress, and age-related diseases. By boosting mitochondrial health, we enhance energy production, reduce oxidative damage, and support key longevity pathways like NAD+ and sirtuins, helping slow down the aging process. 

  • Creatine monohydrate: Primarily known for supporting muscle energy, creatine also plays a direct role in mitochondrial function by helping regenerate ATP, the energy currency of our cells. This supports overall stamina, cognitive function, and physical performance..
  • Calcium Alpha-Ketoglutarate (CaAKG): Supports mitochondrial function and energy production, anti aging effects mediated by histone demethylation, and mTOR inactivation, strong evidence from rodent, early evidence in humans.
  • Nicotinamide Ribose Chloride (NR): Enhances NAD+ levels for mitochondrial health, and epigenetic regulation.
  • Ubiquinol (CoQ10 Reduced): Crucial for mitochondrial energy production.
  • Vitamin B1 (Thiamine HCL): Helps convert carbohydrates into energy.
  • Vitamin B2 (Riboflavin): Supports mitochondrial energy production.
  • Vitamin B3 (Niacinamide): Enhances NAD+ for energy metabolism.
  • Vitamin B5 (D-Calcium Pantothenate): Vital for CoA production, key in energy metabolism.
  • Vitamin B6 (Pyridoxine HCL): Supports amino acid metabolism and energy production.
  • Magnesium citrate anhydrous: Aids ATP production.

 

Cellular Senescence and DNA Repair:

As we age, damaged cells stop dividing and become “senescent,” or zombie cells, contributing to inflammation and thus aging. Cellular senescence and DNA repair are key for longevity—clearing senescent cells and boosting DNA repair pathways help maintain tissue health, prevent age-related diseases, and slow the aging process. Supporting these mechanisms with supplements like fisetin for senescent cell clearance and NAD+ boosters for DNA repair can help keep your body younger, longer!

  • Fisetin (from Smoketree): Senolytic effects, reduces senescent cells.
  • Spermidine (as Spermidine trihydrochloride): Supports autophagy and cellular repair.
  • Genistein (from Japonica): Promotes DNA repair and has anti-senescent properties.
  • Calcium Alpha-Ketoglutarate (CaAKG): Delays cellular senescence.
  • Nicotinamide Ribose Chloride (NR): Enhances DNA repair through NAD+.
  • Vitamin B9 (Calcium L-5-Methyltetrahydrofolate): Supports DNA synthesis and repair.
  • Vitamin B12 (Methylcobalamin): Supports DNA repair.
  • Vitamin D3 (VegD3): Involved in DNA repair mechanisms.
  • Biotin (Vitamin B7): Supports skin, hair, and cellular health, relevant for cellular repair processes.
  • Selenium (as L-selenomethionine): Supports DNA repair mechanisms.

 

Antioxidant Support and Reduction of Inflammation:

Oxidative stress and chronic inflammation speed up aging, leading to diseases like heart disease and Alzheimer’s. Antioxidants and anti-inflammatories help your body fight back! By neutralizing free radicals and reducing inflammation, supplements like glutathione, omega-3s, and curcumin protect your cells and keep you healthier, longer.

  • Grape seed extract (Polyphenols, >90% purity): Strong antioxidant properties.
  • Pomegranate juice extract (>50% polyphenols purity): High in antioxidants.
  • Ceylon cinnamon (Organic): Anti-inflammatory and antioxidant properties.
  • L-Glutathione (Reduced): A powerful antioxidant.
  • Vitamin C (Ascorbic acid): Potent antioxidant and supports immune function.
  • Vitamin E (d-alpha tocopherol): Key antioxidant that protects cell membranes.
  • Omega 3 (ALA): Reduces inflammation and oxidative stress.
  • Astaxanthin (from algae): Strong antioxidant that reduces inflammation.
  • N-Acetyl-L-Cysteine (NAC): Precursor to glutathione, with antioxidant properties.
  • Glucoraphanin (from broccoli): Induces antioxidant defenses via Nrf2 activation.
  • Curcuminoids (75% curcumin, 20% demothoxycurcumin, 5% bisdemothoxycurcumin): Anti-inflammatory and antioxidant properties.
  • Lycopene: Potent antioxidant.
  • Luteolin: Antioxidant and anti-inflammatory properties.
  • Blueberry flakes (freeze-dried): Rich in antioxidants.
  • Ginger extract: Reduces inflammation.
  • Ultra-premium extra virgin olive oil (UP-EVOO): Rich in polyphenols with antioxidant effects.
  • Polyphenols (from olive oil): Antioxidants that reduce inflammation.
  • Oleic acid (from olive oil): Anti-inflammatory and antioxidant.
  • Lutein: Supports eye health and provides antioxidant effects.
  • Zeaxanthin: Works with luteolin to support eye health and reduce oxidative stress.

 

Metabolic Health:

Metabolic health is the foundation of longevity! By improving insulin sensitivity, supporting fat metabolism, and boosting mitochondrial function, you can keep your energy high and reduce the risk of age-related diseases.  Supplements like omega-3s, magnesium, and MCT oil help maintain stable blood sugar, burn fat efficiently, and keep your metabolism running smoothly.

  • Choline (Vitamin B4): Supports lipid metabolism and liver function.
  • Sunflower lecithin (containing phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine): Supports healthy cell membranes and fat metabolism.
  • Taurine: Supports metabolic processes and bile salt formation.
  • L-Lysine HCL: Supports metabolism and protein synthesis.
  • Fiber: Supports digestive health and metabolic regulation.
  • Allulose: Low-calorie sweetener with positive effects on blood glucose.
  • Zinc (as Zinc Bisglycinate): Supports insulin function ,metabolic health and immunity  .
  • Selenium (as L-selenomethionine): Important for thyroid function and metabolism.
  • Iodide (as Potassium Iodide): Supports thyroid health, (optimizing) metabolism.
  • Pea protein isolate: A source of protein for metabolic support.
  • Hemp protein blend: Supports muscle mass and metabolism.
  • Baker’s yeast protein isolate: Protein source supporting metabolic function, (benefits of proteins within the uric acid elevating effect of whole-cell yeast.)
  • Red Yeast Rice (2% Monacolin K): Supports cholesterol metabolism.
  • Glucosamine sulfate potassium: Supports joint health and may influence metabolic function.
  • Monacolin K: Active compound in Red Yeast Rice for cholesterol support.
  • Odorless Garlic Powdered Extract: Supports cardiovascular health and metabolism.

 

Stress Management and Hormonal Support:

Balanced hormones are key to longevity. As we age, hormonal declines can slow metabolism and cause fatigue. Supporting hormonal balance with ashwagandha and omega-3s helps maintain energy levels, reduce stress, and promote overall vitality, enhancing both lifespan and quality of life.

  • Ashwagandha (KSM66 Root Extract): Reduces stress and balances cortisol levels.
  • Rhodiola rosea extract (3% Rosavins/1% Salidroside): Adaptogen that helps with stress management.
  • L-Theanine: Promotes relaxation and reduces stress.
  • L-Lysine HCL: Can reduce anxiety and stress.
  • Magnesium citrate anhydrous: Reduces stress and supports relaxation.
  • Vitamin B6 (Pyridoxine HCL): Supports neurotransmitter function for mood regulation.
  • Vitamin D3 (VegD3): Supports mood and hormonal balance.
  • Vitamin K2 (MK4 and MK7): Supports bone and cardiovascular health, and may help with hormone regulation.
  • Lithium (as Lithium Orotate): Supports mood stabilization.
  • Boron (as Boron Glycinate): Supports hormonal balance, especially testosterone and estrogen.
  • Copper: Essential for hormone production.
  • Sodium hyaluronate (Hyaluronic acid): Supports skin health, which can be influenced by hormonal balance.
  • Vitamin K1: Supports cardiovascular and bone health, indirectly influencing hormonal balance.
  • Manganese (as Manganese Citrate): Supports enzyme function related to stress and energy production.

Detailed content (References here).

Mitochondrial Support and Energy Production:

Creatine monohydrate
Creatine serves as an energy reserve molecule in the muscle helping to sustain performance and increase endurance to exercise., Creatine monohydrate is considered a longevity compound due to its potential benefits in aging populations due to its benefit in increasing and preserving muscle mass and function. Research suggests that creatine supplementation, particularly when combined with resistance training, can improve muscle strength, power, and lean body mass in older adults (Candow et al., 2022; Stares & Bains, 2020). Creatine has shown neuroprotective effects against various neurological disorders and may delay age-related cognitive decline (Baker & Tarnopolsky, 2003; Smith et al., 2014). Studies indicate that creatine supplementation can increase bone mineral density, potentially reducing the risk of osteoporosis (Candow et al., 2022). Furthermore, creatine has been found to enhance muscular endurance and functional capacity in the elderly, even without associated resistance training (Moon et al., 2013). While effect sizes vary across studies, creatine supplementation has demonstrated improvements in muscle strength ranging from 1.4% to 3.2% and increases in lean body mass of 1.4 to 2.1 kg (Buford et al., n.d.; Stares & Bains, 2020).
 
Calcium Alpha-Ketoglutarate (CaAKG)
Calcium Alpha-Ketoglutarate (CaAKG) is considered a longevity compound due to its ability to extend lifespan and improve healthspan in various organisms, research indicates that AKG can reverse the age-related epigenetic changes and preserve youthful gene expression profiles, it is also an essential metabolite for cellular reprogramming and maintaining stem cells (Tran et al., 2018). In mice, CaAKG supplementation increased median lifespan by 12% and reduced frailty by 46% (Asadi Shahmirzadi et al., 2019). AKG acts through multiple mechanisms, including inhibition of ATP synthase and TOR, modulation of DNA and histone demethylation, and reduction of ROS formation (Hakimi Naeini et al., 2023; Chin et al., 2014). It also stabilizes redox homeostasis and improves arterial elasticity in aged mice (Niemiec et al., 2011). AKG's effects are thought to mimic caloric restriction, a well-established longevity intervention (Bayliak et al., 2022). However, its pro-oxidant role suggests a hormetic effect, where moderate increases in ROS levels induce beneficial defensive mechanisms (Bayliak et al., 2022). Current research is exploring AKG's potential in human longevity, with ongoing clinical trials investigating its effects on biological aging markers (Sandalova et al., 2023).
 
Nicotinamide Ribose Chloride (NR)
Nicotinamide Riboside (NR), a form of vitamin B3, is considered a promising longevity compound due to its ability to increase cellular NAD+ levels, which decline with age (Andrei Biță et al., 2023). Studies have shown that NR supplementation can improve mitochondrial function, enhance stem cell activity, and extend lifespan in mice (Zhang et al., 2016). In humans, NR has been found to safely increase NAD+ levels by 40-90% in blood (Heilbronn, 2017; Conze et al., 2019). Further research indicates that NR supplementation may support cardiovascular health by helping to lower blood pressure and reduce aortic stiffness, two key indicators of heart health (Martens et al., 2018). NR supplementation has demonstrated potential benefits for various age-related conditions, including metabolic disorders, neurodegenerative diseases, and muscle degeneration (AlSogair, 2020; Yoshino et al., 2017). Furthermore, NR has been shown to attenuate age-associated changes in hematopoietic stem cells, improving their regenerative capacity (Sun et al., 2021). In yeast, NR promotes Sir2-dependent gene silencing and extends lifespan through increased NAD+ synthesis (Belenky et al., 2007). These findings suggest that NR supplementation may have significant anti-aging effects and potential therapeutic applications.
 
Ubiquinol (CoQ10 Reduced)
Ubiquinol (reduced CoQ10) is considered a longevity compound due to its multifaceted roles in cellular function and protection. As a crucial component of the mitochondrial electron transport chain, it supports energy production (Mantle & Hargreaves, 2019). Ubiquinol's potent antioxidant properties protect against oxidative damage to lipids, proteins, and DNA in cellular membranes and mitochondria (Pobezhimova & Voinikov, 2000; Frei et al., 1990). Studies in roundworms have shown that manipulating CoQ levels can extend lifespan (Rodríguez-Aguilera et al., 2005; Yang et al., 2009). In humans, CoQ10 supplementation has demonstrated significant benefits in various age-related conditions. Notably, it reduced mortality by approximately 50% in cardiovascular disease patients and the elderly (Mantle & Hargreaves, 2019). Additionally, there’s emerging evidence that ubiquinol may improve both male and female fertility, particularly in older individuals or those with certain fertility issues (Sood et al., 2024). CoQ10 also shows promise in managing diabetes, kidney disease, liver inflammation, and neurodegenerative disorders (Dhanasekaran & Ren, 2005; Ernster et al., 1995). These diverse effects contribute to its potential as a longevity-promoting compound.
 
Vitamin B1 (Thiamine HCL)
Vitamin B1 (thiamine) is recognized as a critical component for longevity, playing essential roles in energy metabolism and protein homeostasis. Thiamine deficiency has been associated with various health issues, including heart failure and septic shock (DiNicolantonio et al., 2013; Moskowitz & Donnino, 2020). Research suggests that thiamine supplementation can improve cardiac function and alleviate symptoms in patients with heart failure (DiNicolantonio et al., 2013). Studies in animal models have shown that thiamine and its derivatives offer protective effects against carbonyl stress, oxidative stress, and mitochondrial toxins (Mehta et al., 2008). The amyloid-binding compound thioflavin T, which shares structural similarities with thiamine, has been shown to extend lifespan and slow aging in roundworms by maintaining protein homeostasis (Alavez et al., 2011). Additionally, thiamine's role in cell metabolism has been highlighted, suggesting potential therapeutic strategies (Zastre et al., 2013). Given modern lifestyles, which may increase thiamine needs beyond current RDAs, adequate supplementation is increasingly important(Marrs & Lonsdale, 2021).
 
Vitamin B2 (Riboflavin)
Vitamin B2 (riboflavin) is increasingly recognized for its potential as a longevity compound due to its roles in metabolic health and oxidative stress reduction. In *Caenorhabditis elegans*, riboflavin depletion enhances lifespan through mechanisms involving FOXO/daf-16 and AMPK (Armen Yerevanian et al., 2022). Lifelong riboflavin supplementation in *Drosophila melanogaster* significantly prolonged lifespan (Log rank χ2=16.677, P<0.001) and improved reproductive capacity, highlighting its anti-aging effects (Yingxin Zou et al., 2016). Riboflavin's antioxidant properties contribute to its protective effects against oxidative stress, which is linked to chronic diseases (M. Ashoori & A. Saedisomeolia, 2014; Nafisa Olfat et al., 2022). Additionally, riboflavin regulates energy metabolism, further supporting its role in healthspan and longevity (Eulália Rebeca da Silva-Araújo et al., 2024). Overall, riboflavin's multifaceted biological functions underscore its potential as a longevity-promoting nutrient (Nittiya Suwannasom et al., 2020; A. C. S. Souza et al., 2005).
 
Vitamin B3 (Niacinamide)
Vitamin B3 (niacinamide) is considered a longevity compound due to its role as a precursor for NAD+, a critical coenzyme in cellular metabolism and aging processes (Xu & Sauve, 2010). Niacinamide enhances cell survival and longevity by modulating cellular targets such as mitochondrial membrane potential, PARP, Akt, and caspases (Li et al., 2006; Jasar et al., 2015). It also regulates sirtuins, which are involved in cellular processes like transcription, DNA repair, and senescence (Maiese et al., 2009). In yeast models, increased expression of PNC1, which deaminates nicotinamide, is necessary and sufficient for lifespan extension by calorie restriction (Anderson et al., 2003). However, high concentrations of nicotinamide can inhibit Sir2 and SIRT1, potentially accelerating aging (Bitterman et al., 2002). Dietary supplementation with NAD+ precursors like niacinamide is considered a promising strategy to prevent age-associated NAD+ decline and attenuate metabolic defects common in aging (Orlandi et al., 2020).
 
Vitamin B5 (D-Calcium Pantothenate)
Vitamin B5 (pantothenic acid) is considered a longevity compound due to its various beneficial effects. Studies have shown that B5 supplementation can increase lifespan in mice by 18.8% (Pelton & Williams, 1958). It is classified as a "longevity vitamin" essential for long-term health (Ames, 2018). B5 plays a crucial role in coenzyme A synthesis, impacting energy metabolism and over 70 enzymatic pathways (Sampedro et al., 2015). It has demonstrated potential in improving wound healing and modulating immune responses (Gheita et al., 2020). B5 supplementation enhances the efficacy of cancer immunotherapy (Bourgin et al., 2022). Cerebral B5 deficiency has been linked to metabolic perturbations in Huntington's disease (Patassini et al., 2019). The pharmacokinetics of oral B5 supplementation have been characterized, showing dose-dependent absorption and a long half-life of 225 hours (Rao et al., 2021). These findings highlight the importance of B5 in promoting longevity and overall health.
 
Vitamin B6 (Pyridoxine HCL)
Vitamin B6 is a versatile compound involved in numerous biochemical reactions and cellular processes, making it potentially beneficial for longevity (Mooney et al., 2009; Hellmann & Mooney, 2010). It functions as an enzymatic cofactor and a potent antioxidant, rivaling carotenoids and tocopherols in quenching reactive oxygen species (Mooney et al., 2009; Stach et al., 2021). Vitamin B6 supplementation has been shown to reduce core body temperature in rats, possibly indicating decreased metabolic rate, which may have implications for aging research (Lindseth & Hicks, 1982). While direct evidence for cognitive benefits in humans is limited (Malouf & Evans, 2003; Malouf & Grimley Evans, 2003), vitamin B6 is involved in homocysteine metabolism, and deficiency is associated with elevated homocysteine levels, a risk factor for cardiovascular disease and potentially Alzheimer's disease (Spinneker et al., 2007). Further research is needed to fully elucidate the potential longevity benefits of vitamin B6 supplementation in humans.
 
Magnesium citrate anhydrous
Magnesium citrate anhydrous is considered a longevity compound due to its superior bioavailability compared to other forms like magnesium oxide (Kappeler et al., 2017). Magnesium plays a crucial role in various physiological processes and is linked to all hallmarks of aging (Dominguez et al., 2024). Chronic magnesium deficiency, common in older adults, leads to oxidative stress and low-grade inflammation, contributing to age-related diseases (Barbagallo & Dominguez, 2018). Dietary magnesium supplementation has shown promising results in extending lifespan and improving metabolic health in animal models (Fan et al., 2021; Villa-Bellosta, 2020). Magnesium acts as an antioxidant, protects mitochondria, and may help maintain telomere length (Barbagallo & Dominguez, 2010; Rowe, 2012). While specific effect sizes on longevity outcomes in humans are not provided, maintaining optimal magnesium balance throughout life may contribute to healthy aging and potentially extend healthspan (Deledda et al., 2022).
 
Cellular Senescence and DNA Repair:
Fisetin (from Smoketree)
Fisetin, a flavonoid found in fruits and vegetables, has emerged as a promising longevity compound. Studies have shown that fisetin extends both mean and maximum lifespan in animal models (Park et al., 2022; Yousefzadeh et al., 2018). It exhibits senolytic properties, reducing senescent cell burden and improving tissue homeostasis in aged mice (Shafique et al., 2021; Yousefzadeh et al., 2018). Fisetin demonstrates antioxidant, anti-inflammatory, and neuroprotective effects (Ansari et al., 2024; Kim et al., 2012). In mice, fisetin treatment improved physical activity, cognitive function, and metabolic parameters (Ansari et al., 2024). It also showed potential in mitigating age-related diseases, including Parkinson's disease and diabetes-related inflammation (Park et al., 2022; Kim et al., 2012). Despite its promising effects, fisetin's clinical application is limited by poor bioavailability, necessitating the development of improved delivery strategies (Mehta et al., 2018; Grynkiewicz & Demchuk, 2019). Further research, including human clinical trials, is needed to fully elucidate fisetin's potential as a longevity-promoting compound.
 
Spermidine (as Spermidine trihydrochloride)
Spermidine, a natural polyamine, has emerged as a promising longevity compound with significant effects across various species. It extends lifespan in yeast, nematodes, flies, and human immune cells (Eisenberg et al., 2009). In mice, spermidine supplementation reduces age-related oxidative protein damage and postpones age-associated disorders like cardiovascular disease and neurodegeneration (Hofer et al., 2022). The primary mechanism of spermidine's geroprotective action is through the induction of autophagy, a crucial cellular process for recycling dysfunctional components (Madeo et al., 2010). Spermidine also acts via other pathways, including inflammation reduction, lipid metabolism regulation, and cell growth modulation (Minois, 2014). In humans, spermidine levels decline with age, but increased dietary intake is associated with reduced mortality from cardiovascular diseases and cancer (Madeo et al., 2018). Notably, spermidine supplementation in mice has shown cardioprotective effects, reversing aging-associated cardiac dysfunction (Tong & Hill, 2017). These findings highlight spermidine's potential as a universal anti-aging intervention.
 
Genistein (from Japonica)
Genistein, a phytoestrogen found in soy, is considered a longevity compound due to its diverse biological activities. Studies in Caenorhabditis elegans have shown that genistein significantly extends lifespan under normal and stress conditions (Lee et al., 2015; Zhang et al., 2023). It acts as a multimodal agent, exhibiting antioxidant, anti-inflammatory, and anti-amyloid-β properties (Mas Bargues et al., 2022). Genistein upregulates antioxidant genes, including MnSOD and GPx, through estrogen receptor-mediated activation of ERK1/2 and NFκB pathways (Borrás et al., 2006; Viña et al., 2008). This upregulation leads to reduced oxidative stress and increased stress resistance (Viña et al., 2006). Additionally, genistein modulates various longevity-associated pathways, including insulin/IGF-1 signaling, heat shock proteins, and MAPK (Zhang et al., 2023). Its protective effects extend to cardiovascular health, cancer prevention, and age-related diseases (Sharifi-Rad et al., 2021; Mazumder & Hongsprabhas, 2016).
 
Calcium Alpha-Ketoglutarate (CaAKG)
Calcium Alpha-Ketoglutarate (CaAKG) is considered a longevity compound due to its ability to extend lifespan and improve healthspan in various organisms. In mice, CaAKG supplementation increased median lifespan by 12% and reduced frailty by 46% (Asadi Shahmirzadi et al., 2019). AKG acts through multiple mechanisms, including inhibition of ATP synthase and TOR, modulation of DNA and histone demethylation, and reduction of ROS formation (Hakimi Naeini et al., 2023; Chin et al., 2014). It also stabilizes redox homeostasis and improves arterial elasticity in aged mice (Niemiec et al., 2011). AKG's effects are thought to mimic caloric restriction, a well-established longevity intervention (Bayliak et al., 2022). However, its pro-oxidant role suggests a hormetic effect, where moderate increases in ROS levels induce beneficial defensive mechanisms (Bayliak et al., 2022). Current research is exploring AKG's potential in human longevity, with ongoing clinical trials investigating its effects on biological aging markers (Sandalova et al., 2023).
 
Nicotinamide Ribose Chloride (NR)
Nicotinamide Riboside (NR), a form of vitamin B3, is considered a promising longevity compound due to its ability to increase cellular NAD+ levels, which decline with age (Andrei Biță et al., 2023). Studies have shown that NR supplementation can improve mitochondrial function, enhance stem cell activity, and extend lifespan in mice (Zhang et al., 2016). In humans, NR has been found to safely increase NAD+ levels by 40-90% in blood (Heilbronn, 2017; Conze et al., 2019). NR supplementation has demonstrated potential benefits for various age-related conditions, including metabolic disorders, neurodegenerative diseases, and muscle degeneration (AlSogair, 2020; Yoshino et al., 2017). Furthermore, NR has been shown to attenuate age-associated changes in hematopoietic stem cells, improving their regenerative capacity (Sun et al., 2021). In yeast, NR promotes Sir2-dependent gene silencing and extends lifespan through increased NAD+ synthesis (Belenky et al., 2007). These findings suggest that NR supplementation may have significant anti-aging effects and potential therapeutic applications.
 
Vitamin B9 (Calcium L-5-Methyltetrahydrofolate)
Vitamin B9, particularly in its active form 5-methyltetrahydrofolate (5-MTHF), is considered a longevity compound due to its crucial role in one-carbon metabolism and DNA methylation. Studies have shown that regulation of the folate cycle is a shared causal mechanism of longevity and proteoprotection in C. elegans and mice (Annibal et al., 2020). 5-MTHF supplementation has been found to improve endothelial function and decrease vascular superoxide production in human vessels (Antoniades et al., 2006). Longitudinal studies have associated higher folate consumption with longer leukocyte telomere length, a marker of biological aging (Lee et al., 2017). The folate cycle is also involved in DNA synthesis, amino acid homeostasis, and epigenetic regulation (Lyon et al., 2020). While specific effect sizes vary across studies, the evidence consistently supports the importance of folate in maintaining health and potentially extending lifespan. However, it's important to note that excessive intake may have negative effects (Scaglione & Panzavolta, 2014).
 
Vitamin B12 (Methylcobalamin)
Vitamin B12 (methylcobalamin) is considered a longevity compound due to its crucial roles in DNA synthesis, epigenetic regulation, and mitochondrial function (Simonenko et al., 2024). It helps maintain telomere length, a key marker of biological aging (Praveen et al., 2022). B12 deficiency is associated with various age-related diseases and increased mortality (Hughes et al., 2013). Supplementation with B12 has shown protective effects against glutamate cytotoxicity in neurons (Akaike et al., 1993) and can enhance adaptive capacity to dietary changes, potentially extending lifespan (Nair et al., 2021). As a redox-active compound, high-dose B12 may reduce oxidative stress (Offringa et al., 2021). While specific effect sizes on longevity outcomes are not provided in these studies, B12's impact on telomere length and its antioxidant properties suggest a positive influence on aging processes (Yıldırım & Ekici, 2023). However, more extensive clinical trials are needed to validate these correlations and determine optimal dosages for longevity benefits (Butola et al., 2020).
 
Vitamin D3 
Vitamin D3 has emerged as a potential longevity compound, with studies demonstrating its ability to extend lifespan in model organisms. In C. elegans, vitamin D3 supplementation increased lifespan by up to 39% (Messing et al., 2013) and promoted protein homeostasis (Mark et al., 2016). Similar effects were observed in Drosophila, although the benefits were diet-dependent (Jin et al., 2024). Vitamin D3's longevity-promoting effects are attributed to its role in regulating stress response pathways, innate immunity, and metabolism (Huggins & Farris, 2022; Mark et al., 2016). In humans, vitamin D deficiency is associated with age-related diseases and increased mortality risk (Pérez-López et al., 2011). Vitamin D supplementation may improve immunocompetence and promote healthy aging by modulating the epigenome and transcriptome of immune cells (Carlberg & Velleuer, 2024). Large-scale clinical trials are underway to investigate vitamin D's potential to reduce all-cause mortality (Garay, 2021), which could provide definitive evidence for its role as a longevity compound.
 
Biotin (Vitamin B7)
Biotin (vitamin B7) has emerged as a potential longevity compound due to its diverse roles in cellular processes. Studies have shown that biotin deficiency in Drosophila increased lifespan by 30% and enhanced stress resistance (Smith et al., 2007). Biotin is crucial for carboxylation reactions, gene regulation, and energy production (Scott, 2020). Overexpression of SIRT1, a longevity regulator, in adipose tissue alleviates age-associated biotin accumulation and improves insulin sensitivity and lipid metabolism (Xu et al., 2013). Pharmacological doses of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity through transcriptional, translational, and post-translational mechanisms (Riverón-Negrete & Fernández-Mejía, 2017). However, biotin supplementation is unnecessary for most individuals following a Western diet (John et al., 2019; Lipner, 2018). Biotin's role as a potential "longevity vitamin" is supported by its function in protecting against future damage and reducing the risk of age-associated diseases (Ames, 2018).
 
Selenium (as L-selenomethionine)
Selenium (Se) is considered a longevity compound due to its role in antioxidant defense and metabolic regulation. While Se deficiency can paradoxically promote longevity through stress-response hormesis (Zhang et al., 2018), supplementation with selenomethionine (SeMet) has shown beneficial effects on healthspan. SeMet supplementation protects against diet-induced obesity and alters plasma levels of IGF-1, FGF-21, adiponectin, and leptin in mice (Plummer et al., 2021). In Caenorhabditis elegans, N-γ-(L-Glutamyl)-L-selenomethionine enhances stress resistance and ameliorates aging indicators via the selenoprotein TRXR-1 (Chang et al., 2017). Se's antioxidant properties may remodel physiological changes caused by oxidative stress, potentially leading to disease prevention and healthy aging (Bjørklund et al., 2022). However, the relationship between Se status and longevity is complex, with both deficiency and excess potentially impacting health outcomes (Yim et al., 2019; Robberecht et al., 2019). Further research is needed to fully elucidate Se's role in aging and longevity.
 
Antioxidant Support and Reduction of Inflammation:
Grape seed extract (Polyphenols, >90% purity)
Grape seed extract (GSE), rich in polyphenols, is considered a longevity compound due to its potent antioxidant and anti-inflammatory properties. GSE has been shown to extend lifespan in rats by improving multi-organ function and reducing oxidative stress (Jebari et al., 2021). Procyanidin C1, a component of GSE, increased healthspan and lifespan in mice by targeting senescent cells (Xu et al., 2021). Grape polyphenols, including resveratrol, catechins, and anthocyanins, modulate aging hallmarks such as oxidative damage, inflammation, and cell senescence (Russo et al., 2019). These compounds exhibit cardioprotective effects by reducing LDL oxidation and platelet aggregation (Leifert & Abeywardena, 2008). Additionally, grape polyphenols demonstrate anticancer properties through various mechanisms, including increased reactive oxygen species production and modulation of key molecular pathways (Karami et al., 2018). The antioxidant power of proanthocyanidins in grape seeds is reported to be 20 times greater than vitamin E and 50 times greater than vitamin C (Shi et al., 2003).
 
Pomegranate juice extract (>50% polyphenols purity)
Pomegranate juice and extracts, rich in polyphenols, have shown promising longevity-promoting effects in various studies. In Caenorhabditis elegans, pomegranate juice increased lifespan by 56% and reduced intestinal fat deposition by 68% (Zheng et al., 2017). Similar lifespan extension was observed in Drosophila melanogaster, with an 18% increase in male flies and improved stress resistance (Balasubramani et al., 2014). The health benefits of pomegranate are attributed to its high polyphenol content, including ellagitannins, anthocyanins, and flavonoids (Fahmy et al., 2020). These compounds exhibit antioxidant, anti-inflammatory, and neuroprotective properties (Mackler et al., 2013). In a mouse model of Alzheimer's disease, pomegranate juice decreased amyloid load by approximately 50% and improved cognitive function (Hartman et al., 2006). Human studies have shown that pomegranate juice and extracts provide similar bioavailability of ellagitannin metabolites (Seeram et al., 2008), suggesting potential for translation of these benefits to humans.
 
Ceylon cinnamon (Organic)
Ceylon cinnamon (Cinnamomum zeylanicum) is considered a longevity compound due to its diverse health benefits. It exhibits anti-inflammatory properties, reducing inflammatory signaling and angiogenesis (Lucas et al., 2021). Ceylon cinnamon can lower blood glucose, blood pressure, and serum cholesterol levels (Ranasinghe et al., 2013). It also demonstrates antioxidant, antimicrobial, and neuroprotective effects, potentially inhibiting tau aggregation in Alzheimer's disease (Frydman-Marom et al., 2011; Rao & Gan, 2014). The main bioactive compounds, cinnamaldehyde and o-methoxycinnamaldehyde, show potent anti-inflammatory activity in vitro (Gunawardena et al., 2015). Cinnamon extract extended lifespan in Drosophila melanogaster, partly through insulin signaling (Schriner et al., 2014). While specific effect sizes vary across studies, cinnamon's potential to prevent diseases and improve health is well-documented (Rahayu et al., 2021; Senevirathne et al., 2022). However, more human trials are needed to confirm these benefits and determine optimal dosages.
 
L-Glutathione (Reduced)
L-Glutathione (Reduced) is recognized as a longevity compound due to its essential roles in cellular defense against oxidative stress and its involvement in various metabolic processes. It acts as a master antioxidant, protecting cells from reactive oxygen species and maintaining redox homeostasis (C. Lang, 2001; Domenico Lapenna, 2023). GSH levels decline with age, correlating with increased susceptibility to diseases, while higher GSH levels in healthy elderly individuals suggest a link to enhanced healthspan and lifespan (Domenico Lapenna, 2023). Additionally, GSH is crucial for detoxification and cellular signaling, contributing to apoptosis and ferroptosis regulation (A. Narayanankutty et al., 2019; T. Homma & J. Fujii, 2015). Therapeutic strategies aimed at boosting GSH levels, such as using precursors like N-acetyl cysteine, show promise in counteracting aging-related decline and improving health outcomes (G. Enns & T. Cowan, 2017; C. Labarrere & G. Kassab, 2022).
 
Vitamin C (Ascorbic acid)
Vitamin C (ascorbic acid) is considered a longevity compound due to its antioxidant properties and diverse physiological roles. Studies in animal models have shown that vitamin C supplementation can increase lifespan, though results vary depending on species and dosage (Pallauf et al., 2013). In Gulo-/- mice, vitamin C supplementation increased lifespan, modulated metabolic and cytokine profiles, and alleviated hepatic endoplasmic reticulum stress (Aumailley et al., 2016). Vitamin C plays crucial roles in collagen synthesis, immune function, and protection against oxidative damage (Meščić Macan et al., 2019; Iqbal et al., 2004). It has been associated with reduced risk of chronic diseases and may have neuroprotective effects in Alzheimer's disease (Monacelli et al., 2017). However, its effects on human longevity remain unclear, with some studies showing conflicting results (Sato et al., 2024). Vitamin C's potential as a longevity compound may be due to its ability to modulate gene expression, cellular function, and epigenetic regulation (Duarte & Lunec, 2005; Pehlivan, 2017).
 
Vitamin E (d-alpha tocopherol)
Vitamin E, particularly α-tocopherol, has been investigated for its potential longevity-enhancing properties. While some studies have shown promising results, the overall evidence is mixed. In cultured human diploid cells, initial findings suggested a significant lifespan extension with vitamin E supplementation (Packer & Smith, 1974), but subsequent attempts failed to replicate these results (Packer & Smitht, 1977). In mice, lifelong dietary α-tocopherol supplementation increased median lifespan by 15%, possibly through anti-cancer effects (Banks et al., 2010). However, in invertebrate models, the effects were less pronounced, with only γ-tocopherol slightly extending lifespan in nematodes (Zou et al., 2007). Vitamin E's role in longevity appears to be complex, with potential benefits in seed longevity (Sattler et al., 2004) and interactions with phosphorus availability in plants (Simancas & Munné‐Bosch, 2015). Recent studies have also highlighted potential negative effects, particularly on bone health (Ochi & Takeda, 2014), calling into question its universal "anti-aging" properties.
 
Omega 3 (ALA)
Omega-3 fatty acids, particularly alpha-linolenic acid (ALA), have been associated with various health benefits and longevity. ALA has been shown to extend lifespan in C. elegans through activation of NHR-49/PPARα and SKN-1/Nrf2 transcription factors (Qi et al., 2017). It also demonstrates cardioprotective effects, including lowering blood pressure and reducing coronary heart disease risk in men (Simopoulos, 2004). ALA intake is linked to inhibition of platelet aggregation and regulation of arachidonic acid metabolism (Simopoulos, 2004). While ALA's conversion to EPA and DHA is limited in humans, it still plays a crucial role in maintaining tissue long-chain n-3 fatty acid levels (Barceló-Coblijn & Murphy, 2009). ALA has also shown neuroprotective properties in rodent models of stroke and anti-depressant-like activity, possibly through increasing brain-derived neurotrophic factor (BDNF) (Blondeau et al., 2015). However, more research is needed to fully understand ALA's effects on human health and longevity.
 
Astaxanthin (from algae)
Astaxanthin, a powerful antioxidant carotenoid derived from algae, has shown promising longevity-enhancing properties. Studies in C. elegans demonstrated that astaxanthin extended lifespan by 16-30% through modulation of the Ins/IGF-1 signaling pathway and mitochondrial complex III biogenesis (Yazaki et al., 2011; Hoffman et al., 2019). Its neuroprotective effects are attributed to its ability to cross the blood-brain barrier, increase BDNF levels, and attenuate oxidative damage (Sorrenti et al., 2020). Astaxanthin also activates longevity-related genes such as FOXO3, Sirt1, and Klotho (Sorrenti et al., 2020). In fruit flies, astaxanthin supplementation extended lifespan and improved locomotor function in SOD-deficient mutants (Huangfu et al., 2013). Its anti-inflammatory properties involve suppression of the NF-κB pathway and reduction of pro-inflammatory cytokines (Medoro et al., 2023). These multifaceted effects on oxidative stress, inflammation, and cellular signaling pathways contribute to astaxanthin's potential as a geroprotector and neuroprotective agent (Sztretye et al., 2019; Galasso et al., 2018).
 
N-Acetyl-L-Cysteine (NAC)
N-Acetyl-L-Cysteine (NAC) is considered a longevity compound due to its antioxidant and anti-inflammatory properties. In C. elegans, NAC supplementation extended mean lifespan by up to 30.5% and maximum lifespan by 8 days, while increasing resistance to environmental stressors (Seung-Il Oh et al., 2015). NAC acts as a precursor to glutathione, a crucial antioxidant, and can directly scavenge certain oxidant species (Aldini et al., 2018). It has shown potential benefits in various neurodegenerative diseases and cognitive aging (Tardiolo et al., 2018; Buchanan, 2020). However, the relationship between NAC and longevity is complex. Some studies suggest that chronic administration of NAC can accelerate aging in C. elegans by perturbing gene expression and inhibiting skn-1-mediated transcription (Gusarov et al., 2021). The effects of NAC on lifespan appear to follow an inverted U-shaped dose-response curve, with both positive and negative outcomes depending on concentration and conditions (Desjardins et al., 2016).
 
Glucoraphanin (from broccoli)
Glucoraphanin, found in broccoli, is a precursor to sulforaphane, a potent activator of Nrf2, which regulates antioxidant and detoxification pathways (James et al., 2012; Xu et al., 2018). Sulforaphane has shown potential in mitigating obesity, insulin resistance, and inflammation (Xu et al., 2018). It induces phase II enzymes, particularly quinone reductase, with a 3-4.5 fold increase observed in murine hepatoma cells (Hwang & Jeffery, 2005). However, the effects of glucoraphanin are complex, as it can also induce phase I enzymes and generate reactive oxygen species (Paolini et al., 2003). Clinical trials have explored sulforaphane's bioavailability and efficacy, but challenges remain in determining optimal dosage and administration routes (Yagishita et al., 2019). While broccoli sprout supplements are available, their effectiveness depends on retaining both glucoraphanin and myrosinase activity (Houghton et al., 2013). Further research is needed to fully understand sulforaphane's mechanisms of action and develop validated biomarkers for human studies (Yagishita et al., 2019).
 
Curcuminoids (75% curcumin, 20% demothoxycurcumin, 5% bisdemothoxycurcumin)
Curcuminoids, particularly curcumin, have shown promising anti-aging effects in various studies. Research indicates that curcumin can extend the lifespan of model organisms like C. elegans, D. melanogaster, and mice (Shen et al., 2013; Liao et al., 2011). This longevity-promoting effect is attributed to curcumin's antioxidant and anti-inflammatory properties, which help reduce oxidative stress and cellular damage associated with aging (Izadi et al., 2024; Zia et al., 2020). Curcumin modulates key signaling pathways involved in aging, such as IIS, mTOR, and FOXO (Zia et al., 2020). It also enhances superoxide dismutase (SOD) activity and decreases lipofuscin levels (Shen et al., 2013). In C. elegans, curcumin extended lifespan by 39% and reduced intracellular reactive oxygen species (Liao et al., 2011). Additionally, curcumin has shown neuroprotective effects and potential in preventing age-related diseases (Benameur et al., 2021; Amalraj et al., 2016). These findings suggest that curcuminoids may be promising candidates for promoting healthy aging and longevity.
 
Lycopene
Lycopene, a carotenoid found in red fruits and vegetables, is considered a longevity compound due to its potent antioxidant properties (Petyaev, 2016). It has been shown to protect against oxidative stress, inflammation, and various age-related diseases (Abir et al., 2023). Low serum lycopene levels are strongly predictive of all-cause mortality and poor cardiovascular outcomes (Petyaev, 2016). Studies have demonstrated lycopene's protective effects on the cardiovascular system, reducing the risk of myocardial infarction and lowering blood pressure (Przybylska, 2019). It may also help prevent certain cancers, including prostate, lung, and breast cancer (Przybylska, 2019). While some studies suggest a positive relationship between lycopene and maintained cognitive function (Crowe-White et al., 2019), evidence for its effects on dementia is limited. Lycopene's health benefits are primarily attributed to its antioxidant activity, but its pleiotropic effects contribute to its overall impact on human health (Kulawik et al., 2023; Caseiro et al., 2020).
 
Luteolin
Luteolin, a flavonoid found in various plants, has emerged as a promising longevity compound due to its diverse biological effects. Studies have shown that luteolin can extend lifespan in model organisms like C. elegans and D. melanogaster (Lashmanova et al., 2017). Its geroprotective properties are attributed to its potent antioxidant and anti-inflammatory activities (Xu et al., 2019; Singh et al., 2024). Luteolin modulates multiple signaling pathways, including NF-κB, MAPK, and Nrf-2, which are crucial for cellular health and longevity (Zhu et al., 2024). It exhibits neuroprotective effects, potentially benefiting age-related neurodegenerative disorders (Nabavi et al., 2015). Luteolin also shows promise in mitigating skin aging and inflammation (Gendrisch et al., 2020). While specific effect sizes on longevity outcomes vary across studies, luteolin's multifaceted actions on oxidative stress, inflammation, and cellular signaling pathways contribute to its potential as a geroprotector (Caporali et al., 2022; Theoharides, 2021).
 
Blueberry flakes (freeze-dried)
Blueberry extracts have shown promising longevity-promoting effects in various model organisms. In C. elegans, blueberry polyphenols increased lifespan by up to 44.4% and improved stress resistance (Wilson et al., 2006; Wang et al., 2018). Similarly, in Drosophila, blueberry extracts extended mean lifespan by 10% (Peng et al., 2012). These effects are attributed to the high antioxidant capacity of blueberries, particularly their polyphenol content (Silva et al., 2018). Mechanistically, blueberry compounds modulate aging-related pathways, including oxidative stress response, inflammation, and telomere maintenance (Li et al., 2018). They upregulate antioxidant genes like SOD and CAT, and interact with longevity-associated genes such as daf-16 (Wang et al., 2018; Peng et al., 2012). While most studies have been conducted in model organisms, the potential health benefits of blueberries in humans are supported by their high polyphenol content and antioxidant properties (Kelly et al., 2017; Kowalska, 2021).
 
Ginger extract
Ginger extract has shown promising longevity-promoting properties in various studies. In C. elegans, ginger extract extended lifespan by 23.16% (Xu et al., 2022), while shell ginger increased lifespan by 22.6% in animals (Teschke & Xuan, 2018). The compound 6-gingerol, isolated from ginger, demonstrated potent longevity-promoting activity and enhanced stress resistance in C. elegans (Lee et al., 2018). Ginger extract exhibits antioxidant, anti-inflammatory, and anticancer properties (Ozkur et al., 2022). It inhibits beta-amyloid peptide-induced inflammation in human monocytic cells (Grzanna et al., 2004) and reduces plasma cholesterol and atherosclerosis development in mice (Fuhrman et al., 2000). Gingerenone A, a component of ginger extract, shows senolytic properties by selectively eliminating senescent cells (Moaddel et al., 2022). Additionally, ginger extract promotes telomere shortening and cellular senescence in lung cancer cells (Kaewtunjai et al., 2018), suggesting potential anticancer effects.
 
Ultra-premium extra virgin olive oil (UP-EVOO)
Ultra-premium extra virgin olive oil (UP-EVOO) is considered a longevity compound due to its high content of monounsaturated fatty acids and polyphenols, which exhibit antioxidant and anti-inflammatory properties (Trichopoulou & Dilis, 2007; Gaforio et al., 2019). These compounds modulate aging-associated processes by activating Nrf-2 signaling and suppressing NF-κB activation, thus reducing oxidative stress and inflammation (Serreli & Deiana, 2020). EVOO consumption is associated with lower mitochondrial oxidative stress and protection against age-related cognitive decline (Quiles et al., 2006). Studies have shown that EVOO polyphenols, particularly hydroxytyrosol and oleocanthal, inhibit cyclooxygenases and prevent LDL oxidation (Virruso et al., 2014). Regular EVOO intake has been linked to enhanced neuroprotective, anti-atherosclerotic, and anti-cancer properties (Tzekaki et al., 2021). While specific effect sizes vary across studies, the cumulative evidence supports EVOO's role in promoting longevity and reducing the risk of age-related diseases (Martín-Peláez et al., 2013; Rigacci & Stefani, 2016).
 
Polyphenols (from olive oil)
Polyphenols from olive oil, particularly hydroxytyrosol and tyrosol, are considered longevity compounds due to their antioxidant and anti-inflammatory properties (Rigacci & Stefani, 2016; Serreli & Deiana, 2020). These compounds have been shown to activate Nrf-2 signaling and suppress NF-κB activation, modulating cellular pathways related to aging (Serreli & Deiana, 2020). In C. elegans, tyrosol increased lifespan and stress resistance (Cañuelo et al., 2012). Human studies have demonstrated that olive oil polyphenols protect blood lipids from oxidation and improve cardiovascular risk factors (Martín-Peláez et al., 2013; Karković Marković et al., 2019). Additionally, these compounds have shown neuroprotective effects and potential benefits for cognitive function in aging (Giovannelli, 2012). While the evidence for antioxidant effects in humans is growing, with observable benefits at intakes of about 10 mg per day (Raederstorff, 2009), further research is needed to fully elucidate the mechanisms behind their longevity-promoting effects (Gaforio et al., 2019).
 
Oleic acid (from olive oil)
Polyphenols from olive oil, particularly hydroxytyrosol and tyrosol, are considered longevity compounds due to their antioxidant and anti-inflammatory properties (Rigacci & Stefani, 2016; Serreli & Deiana, 2020). These compounds have been shown to activate Nrf-2 signaling and suppress NF-κB activation, modulating cellular pathways related to aging (Serreli & Deiana, 2020). In C. elegans, tyrosol increased lifespan and stress resistance (Cañuelo et al., 2012). Human studies have demonstrated that olive oil polyphenols protect blood lipids from oxidation and improve cardiovascular risk factors (Martín-Peláez et al., 2013; Karković Marković et al., 2019). Additionally, these compounds have shown neuroprotective effects and potential benefits for cognitive function in aging (Giovannelli, 2012). While the evidence for antioxidant effects in humans is growing, with observable benefits at intakes of about 10 mg per day (Raederstorff, 2009), further research is needed to fully elucidate the mechanisms behind their longevity-promoting effects (Gaforio et al., 2019).
 
Lutein
Lutein, a carotenoid found in dark green leafy vegetables and eggs, is considered a longevity compound due to its protective effects on both visual and cognitive function throughout the lifespan (Johnson, 2014). It accumulates in the retina and brain, acting as an antioxidant and blue light filter (Nian & Lo, 2018). Lutein has been shown to extend the lifespan of Drosophila melanogaster by 11.4% through upregulation of antioxidant enzymes (Zhang et al., 2014). In C. elegans, lutein treatment increased resistance to heat and oxidative stress, extending healthspan (Maglioni et al., 2021). Lutein protects human retinal pigment epithelial cells from oxidative stress-induced cellular senescence, a contributor to age-related macular degeneration (Chae et al., 2018). Higher lutein status is associated with better cognitive performance in adults (Johnson, 2014). These findings support lutein's classification as a putative longevity vitamin, potentially reducing the risk of chronic diseases and premature aging (Ames, 2018).
 
Zeaxanthin
Zeaxanthin, a xanthophyll carotenoid, is considered a longevity compound due to its potent antioxidant and anti-inflammatory properties (Ames, 2018; Murillo et al., 2019). It accumulates selectively in eye tissue and the brain, where it may protect against oxidative stress and age-related diseases (Johnson, 2014; Tan et al., 2023). Zeaxanthin has shown particular promise in maintaining eye health, potentially reducing the risk of cataracts, glaucoma, and age-related macular degeneration (Manikandan et al., 2016; Yang et al., 2016). While specific effect sizes are not provided, studies suggest that higher lutein and zeaxanthin status is associated with better cognitive performance in adults (Johnson, 2014). However, more research is needed to fully understand the independent effects of zeaxanthin supplementation on human health and longevity (Mares-Perlman et al., 2002). The potential benefits of zeaxanthin extend beyond eye health, with possible protective effects on the heart, liver, and skin (Murillo et al., 2019; Sztretye et al., 2019).
 
Metabolic Health:
Choline (Vitamin B4)
Choline, an essential nutrient, is considered a longevity compound due to its numerous beneficial effects. Studies have shown that choline supplementation extends lifespan in C. elegans by up to 20% (Liu et al., 2022) and improves stress resistance and cognitive function (Kim et al., 2019). In humans, choline levels decline with age, and supplementation may protect against age-related cognitive decline (Moretti, 2020). Choline's neuroprotective effects are attributed to its role in phospholipid synthesis, neurotransmitter production, and epigenetic regulation through DNA and histone methylation (Blusztajn et al., 2017; Blusztajn & Mellott, 2012). In Alzheimer's disease mouse models, lifelong choline supplementation reduces amyloid-β plaque load by 28% and improves spatial memory (Velazquez et al., 2019). Additionally, choline exhibits antioxidant properties, reduces lipofuscin accumulation, and enhances exercise capacity in aging animals (Merinas-Amo et al., 2017; Liu et al., 2022). These findings suggest that choline supplementation may be a promising strategy for promoting longevity and healthy aging.
 
Sunflower lecithin (containing phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine)
Sunflower lecithin, containing phosphatidylcholine (PC), phosphatidylinositol, and phosphatidylethanolamine, is considered a longevity compound due to its antioxidant properties and effects on cellular function. PC supplementation has been shown to extend lifespan in C. elegans by 24% through DAF-16 activation and reduction of amyloid-beta toxicity (Kim et al., 2019). Lecithin preserves mitochondrial function and protects against age-related hearing loss in rats (Seidman et al., 2002). Phospholipids play critical roles in cell membrane signal transduction and may be involved in preventing diseases like cancer and Alzheimer's (Canty & Zeisel, 2009). The antioxidant effects of lecithin can improve the stability of oils and fats (Nasner, 1985). Estrogen-like compounds in lecithin may contribute to longevity by upregulating antioxidant genes (Viña et al., 2005). Specific lipid profiles are associated with longevity, and dietary lipids influence chromatin regulation in aging (Papsdorf & Brunet, 2019).
 
Taurine
Taurine, a conditionally essential amino acid, has emerged as a potential longevity compound. Studies have shown that taurine levels decline with age in mice, monkeys, and humans (Singh et al., 2023). Supplementation with taurine has been found to increase healthspan in worms, mice, and monkeys, and lifespan in worms and mice (Yadav et al., 2024). Taurine's anti-aging effects are attributed to its role in proper protein folding, reducing cellular senescence, protecting against telomerase deficiency, suppressing mitochondrial dysfunction, decreasing DNA damage, and attenuating inflammaging (Singh et al., 2023; Ito et al., 2015). In Drosophila, taurine repressed age-associated gut hyperplasia by reducing endoplasmic reticulum stress (Du et al., 2021). Epidemiological studies have linked higher taurine intake to lower mortality rates from ischemic heart disease and stroke (Yamori et al., 2009). These findings suggest that taurine deficiency may be a driver of aging, warranting further investigation through clinical trials in humans (Ho et al., 2023).
 
L-Lysine HCL
L-Lysine HCl is considered a longevity compound due to its potential to extend lifespan and improve health outcomes. Lysine supplementation has been shown to alleviate calcium oxalate stress and prolong lifespan in individuals with various disorders (Lin et al., 2021). A year-long study demonstrated that a cocktail including lysine increased lean tissue mass by 1.2% and protein turnover by 12% in elderly individuals (Baier et al., 2009). Lysine plays a role in histone methylation, which can affect lifespan through epigenetic regulation (Han & Brunet, 2012). Additionally, increased fidelity of protein synthesis, which can be influenced by lysine residues in ribosomal proteins, has been linked to extended lifespan in various organisms (Martinez-Miguel et al., 2021). While specific effect sizes for lysine alone are not provided, these studies suggest that lysine supplementation may contribute to longevity through multiple mechanisms, including protein metabolism and epigenetic regulation.
 
Fiber
Dietary fiber is increasingly recognized as a longevity compound due to its multifaceted health benefits. Studies have shown that fiber intake is associated with longer telomeres, corresponding to reduced biological aging by 4.3-5.4 years (Tucker, 2018). Fiber supplementation has been found to extend lifespan in animal models, including Drosophila melanogaster (Beghelli et al., 2024). The mechanisms behind fiber's longevity effects include improved gut microbiota diversity, reduced inflammation, and enhanced antioxidant capacity (Yu et al., 2022; Shi et al., 2024). Specifically, dietary fiber increases beneficial gut bacteria like Bifidobacterium and Lactobacillus while decreasing harmful ones like E. coli (Shi et al., 2024). Fiber intake is also positively associated with butyrate production, which has anti-inflammatory effects and may improve neuroinflammation associated with aging (Cai et al., 2016; Matt et al., 2018). These findings highlight the importance of adequate fiber consumption for healthy aging and longevity (Donini et al., 2009; Cámara et al., 2017).
 
Allulose
Allulose, a rare sugar and epimer of fructose, has emerged as a potential longevity compound due to its calorie restriction mimetic effects. Studies in C. elegans have shown that allulose extends lifespan by 23.8% (p < 0.0001) through dietary restriction mechanisms and increased oxidative stress resistance (T. Shintani et al., 2017). In humans, allulose attenuates postprandial blood glucose levels (Tani Yuma et al., 2023) and enhances fat oxidation (Kimura et al., 2017). It also improves age-associated sarcopenia in mice by regulating IGF-1 and myostatin (Kim et al., 2021). Importantly, allulose generates significantly fewer advanced glycation end-products (AGEs) compared to glucose and fructose, potentially reducing oxidative stress and inflammation (Clarke et al., 2024). These effects are mediated through various pathways, including AMPK activation (T. Shintani et al., 2017), sirtuin signaling (Tomoya Shintani et al., 2019), and insulin pathways (Ingram & Roth, 2020; H. Shintani et al., 2018).
 
Zinc (as Zinc Bisglycinate)
Zinc is considered a longevity compound due to its crucial role in various biological processes. Research suggests that zinc supplementation can improve immune function, antioxidant defense, and metabolic homeostasis in aging organisms (Mocchegiani et al., 2008; Mocchegiani et al., 2007). Zinc deficiency has been linked to accelerated aging, while proper zinc balance may promote healthy aging (Kumar et al., 2016). The intracellular zinc homeostasis is regulated by metallothioneins and zinc transporters, which become dysregulated with age (Mocchegiani et al., 2010). Zinc supplementation in elderly subjects has been shown to restore thymic endocrine activity and innate immune response, potentially increasing lifespan (Mocchegiani et al., 2006). However, the effectiveness of zinc supplementation may depend on individual genetic factors, particularly related to IL-6 and metallothionein polymorphisms (Mocchegiani et al., 2010). Recent research has also explored zinc-boron complexes as potential dietary supplements for longevity (Biță et al., 2023).
 
Selenium (as L-selenomethionine)
Selenium (Se) is considered a longevity compound due to its role in antioxidant defense and metabolic regulation. While Se deficiency can paradoxically promote longevity through stress-response hormesis (Zhang et al., 2018), supplementation with selenomethionine (SeMet) has shown beneficial effects on healthspan. SeMet supplementation protects against diet-induced obesity and alters plasma levels of IGF-1, FGF-21, adiponectin, and leptin in mice (Plummer et al., 2021). In Caenorhabditis elegans, N-γ-(L-Glutamyl)-L-selenomethionine enhances stress resistance and ameliorates aging indicators via the selenoprotein TRXR-1 (Chang et al., 2017). Se's antioxidant properties may remodel physiological changes caused by oxidative stress, potentially leading to disease prevention and healthy aging (Bjørklund et al., 2022). However, the relationship between Se status and longevity is complex, with both deficiency and excess potentially impacting health outcomes (Yim et al., 2019; Robberecht et al., 2019). Further research is needed to fully elucidate Se's role in aging and longevity.
 
Iodide (as Potassium Iodide)
Iodine, particularly in the form of potassium iodide, has been associated with longevity and health benefits. A 20-year follow-up study found that residents in an iodine-replete area had increased longevity compared to those in an iodine-deficient area (Riis et al., 2020). Iodine's antioxidant properties may contribute to its positive effects on various health conditions, including cardiocirculatory and respiratory disorders (Winkler, 2015). In Drosophila melanogaster, diiodomethane increased median lifespan by 29.3% (Massie et al., 1978). Potassium iodide has shown effectiveness in protecting the thyroid from radioactive iodine exposure, with a 100 mg dose blocking at least 95% of thyroid dose in adults (Verger et al., 2001). Interestingly, potassium iodide administration months to years after radiation exposure reduced thyroid cancer risk threefold in children affected by the Chernobyl accident (Grossman & Nussbaum, 2006). However, potential side effects and complications, such as thyroid adenoma, should be considered (Siegal, 1964; Ilin & Nersesyan, 2013).
 
Pea protein isolate
Pea protein isolate is emerging as a potential longevity compound due to its nutritional and functional properties. Studies have shown that pea protein has anabolic effects comparable to milk proteins in older rats, supporting muscle protein metabolism (Salles et al., 2021). It offers health benefits such as high satiety, glycemic control, and blood pressure reduction (Stilling, 2020). Pea protein's high digestibility and amino acid composition make it an efficient protein source for older individuals (Salles et al., 2021). While specific research on pea protein's longevity effects is limited, studies on dietary proteins suggest that plant-based proteins may contribute to healthy aging and longevity (Tavano & da Silva Júnior, 2019). However, the optimal protein intake and source for longevity remain debated, with some research indicating benefits of reduced protein intake or specific amino acid restrictions (Kitada et al., 2019). Further research is needed to elucidate pea protein's long-term impact on muscle health and longevity (Putra et al., 2021).
 
Hemp protein blend
Hemp protein blend is considered a longevity compound due to its nutritional profile and potential health benefits. Hempseed protein contains a well-balanced amino acid composition, comparable to soy protein, and meets most essential amino acid requirements for children (Tang et al., 2006). It exhibits antioxidant, immunomodulatory, hypotensive, hypoglycemic, and lipid-lowering properties in vitro (Santos-Sánchez et al., 2022). A diet incorporating hemp seed has been shown to extend lifespan and improve cognitive function in aged mice, while also protecting against age-related metabolic syndrome and chronic inflammation (Li et al., 2018). Hemp protein's potential longevity-promoting effects may be linked to its ability to induce mitonuclear protein imbalance, which activates the mitochondrial unfolded protein response, a conserved longevity pathway (Houtkooper et al., 2013). Additionally, plant-based diets, which can include hemp protein, are associated with lower mortality rates and improved metabolic and inflammatory profiles in adults (Herpich et al., 2022).
 
Baker’s yeast protein isolate
Baker's yeast protein isolate is considered a longevity compound due to its ability to modulate various cellular processes associated with aging. Studies have shown that yeast-based interventions can extend lifespan by up to threefold in Saccharomyces cerevisiae (Fabrizio et al., 2001). Yeast longevity is strongly associated with up-regulation of oxidative phosphorylation and respiration, and down-regulation of amino acid biosynthesis (Kaya et al., 2015). Lithocholic acid, a bile acid found in yeast, has been identified as a potent anti-aging compound that extends chronological lifespan by modulating mitochondrial membrane lipidome and altering vital mitochondrial processes (Beach et al., 2013; Goldberg et al., 2010). Yeast-based technology is being used as a model for caloric restriction, which has shown promising results in improving human lifespan (Moyad, 2007; Moyad, 2008). Additionally, yeast-derived products have demonstrated potential in enhancing immune function and reducing the incidence and duration of common cold and flu symptoms (Moyad, 2008).
 
Red Yeast Rice (2% Monacolin K)
Red Yeast Rice (RYR), containing Monacolin K, is considered a longevity compound due to its cholesterol-lowering effects and other health benefits. Studies show that 10 mg of Monacolin K daily can reduce LDL-cholesterol by 15-25% in 6-8 weeks (Cicero, 2018). RYR also demonstrates anti-cancer, neuroprotective, and anti-inflammatory properties (Xiong et al., 2019; Monu et al., 2022). It may help prevent colon cancer, acute myeloid leukemia, and neurological disorders like Parkinson's disease (Xiong et al., 2019). Additionally, RYR improves endothelial function and pulse wave velocity, which are biomarkers of vascular aging (Cicero, 2018). However, the efficacy and safety of RYR products vary due to inconsistent Monacolin K content (Dujovne, 2017). While RYR shows promise as a nutraceutical, further research is needed to standardize its composition and fully understand its diverse pharmacological effects (Zhu et al., 2019; Nguyen et al., 2011).
 
Glucosamine sulfate potassium
Glucosamine sulfate potassium is considered a longevity compound due to its potential to extend lifespan and improve health outcomes. Studies in C. elegans demonstrated that glucosamine extended lifespan by up to 30% through autophagy induction (Shintani et al., 2018). Similar effects were observed in aging mice, with glucosamine supplementation increasing mitochondrial biogenesis and improving glucose metabolism (Weimer et al., 2014). In humans, glucosamine use was associated with reduced total mortality (Shintani et al., 2021). For osteoarthritis, glucosamine sulfate showed significant benefits in reducing joint space narrowing and improving symptoms. A 3-year study reported a 54% reduction in disease progression risk (Poolsup et al., 2005) and a 20-25% improvement in symptoms compared to placebo (Pavelka et al., 2002). The patented crystalline glucosamine sulfate formulation demonstrated superior efficacy compared to other forms (Kucharz et al., 2016). Overall, glucosamine sulfate shows promise as a geroprotective agent with multiple health benefits.
 
Monacolin K
Monacolin K, a compound found in red yeast rice, is considered a longevity compound primarily due to its cholesterol-lowering effects. It acts by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis (Xiong et al., 2019; Hou & Sun, 2023). Clinical trials have shown that Monacolin K supplementation significantly reduces LDL and total cholesterol levels, with doses as low as 3 mg/day being effective (Liasi et al., 2024). Beyond lipid-lowering, Monacolin K exhibits anticancer properties, potentially preventing various types of cancer by affecting MAPK, PI3K/AKT, and NF-κB pathways (Monu et al., 2022; Hou & Sun, 2023). It also demonstrates neuroprotective and anti-inflammatory effects (Xiong et al., 2019). Compared to synthetic statins, Monacolin K may have fewer side effects, particularly regarding muscle toxicity (Lee et al., 2013). However, regulatory concerns exist due to its similarity to lovastatin, and further research is needed to establish optimal dosing and long-term safety (Nguyen et al., 2011).
 
Odorless Garlic Powdered Extract
Odorless Garlic Powdered Extract, particularly Aged Garlic Extract (AGE), is considered a longevity compound due to its potent antioxidant and anti-inflammatory properties. AGE contains stable organosulfur compounds like S-allylcysteine, which scavenge reactive oxygen species and enhance cellular antioxidant enzymes (Colín-González et al., 2012; Capasso, 2013). These compounds protect against oxidative damage to DNA, proteins, and lipids, potentially slowing aging processes (Borek, 2001). AGE has shown cardioprotective effects by inhibiting LDL oxidation and suppressing thrombin formation (Fukao et al., 2007). It may also improve cognitive function and increase longevity in animal models (Borek, 2001). Additionally, AGE exhibits anti-inflammatory properties, which could benefit conditions like pulmonary inflammation (Persson & Persson, 2012). The diverse bioactive compounds in garlic demonstrate antioxidant, anti-inflammatory, and protective effects on various organ systems, supporting its potential as a longevity-promoting supplement (Shang et al., 2019; Sharma & Rani, 2022).
 
Stress Management and Hormonal Support:
Ashwagandha (KSM66 Root Extract)
Ashwagandha (Withania somnifera) root extract, particularly KSM-66, is considered a longevity compound due to its diverse health benefits. Studies have shown that it can extend lifespan in C. elegans by approximately 20% (Kumar et al., 2013). Ashwagandha exhibits neuroprotective effects, potentially aiding in the treatment of neurodegenerative disorders like Parkinson's disease (Wongtrakul et al., 2021; Ven Murthy et al., 2010). It has demonstrated antioxidant, anti-inflammatory, and immune-modulating properties (Winters, 2006). In cancer research, Ashwagandha has shown promise in reducing tumor cell proliferation and enhancing the effectiveness of radiation therapy (Winters, 2006). The herb is classified as a rasayana in Ayurvedic medicine, promoting longevity and vitality (Kulkarni & Dhir, 2008; Joshi, 2016). Its active compounds, withanolides, contribute to its broad spectrum of health benefits (Mandal, 2017). While extensive research has been conducted on animal models and in vitro studies, more human trials are needed to fully establish its efficacy as a longevity compound (Kumar et al., 2021).
 
Rhodiola rosea extract (3% Rosavins/1% Salidroside)
Rhodiola rosea extract, particularly its compound salidroside, has shown promising longevity and health-promoting effects. Studies have demonstrated its ability to extend lifespan in various model organisms, including Caenorhabditis elegans (37.1% increase) and Nothobranchius guentheri fish (Jiang et al., 2021; Wang et al., 2018). The extract exhibits adaptogenic, antidepressant, and anxiolytic properties in mice (Perfumi & Mattioli, 2007). Its anti-aging effects are attributed to antioxidant activities, reducing oxidative stress and cellular senescence (Mao et al., 2010). Rhodiola rosea also shows neuroprotective effects in Alzheimer's disease models by activating the PI3K/Akt pathway (Zhang et al., 2016). Furthermore, it demonstrates anticancer properties, inhibiting bladder cancer cell growth via mTOR pathway modulation and autophagy induction (Liu et al., 2012). The extract's beneficial effects are mediated through various pathways, including insulin/IGF signaling and SKN-1, promoting stress resistance and longevity (Jiang et al., 2021; Li et al., 2017).
 
L-Theanine
L-Theanine, an amino acid found in tea, has shown promising longevity-enhancing properties. In C. elegans, L-theanine extended lifespan by up to 3.6% at concentrations of 100 nM to 10 μM (Zarse et al., 2012). It demonstrates antioxidant and anti-inflammatory effects, potentially contributing to its anti-aging capabilities (Corrêa et al., 2018; Li et al., 2022). In aging rats, L-theanine increased antioxidant enzyme activities and decreased pro-inflammatory factors, protecting against liver aging (Zeng et al., 2019). It also attenuated memory impairments in a genetic aging model by modulating signaling pathways (Nguyen et al., 2019). In mice, L-theanine consumption (5-6 mg/kg) suppressed shortened lifespan, cerebral atrophy, and cognitive dysfunction induced by chronic psychosocial stress (Unno et al., 2011). While animal studies show promise, more longitudinal observational studies and human clinical trials are needed to establish L-theanine's efficacy in promoting healthy aging in humans (Song et al., 2011; Williams et al., 2019).
 
L-Lysine HCL
L-Lysine HCl is considered a longevity compound due to its potential to extend lifespan and improve health outcomes. Lysine supplementation has been shown to alleviate calcium oxalate stress and prolong lifespan in individuals with various disorders (Lin et al., 2021). A year-long study demonstrated that a cocktail including lysine increased lean tissue mass by 1.2% and protein turnover by 12% in elderly individuals (Baier et al., 2009). Lysine plays a role in histone methylation, which can affect lifespan through epigenetic regulation (Han & Brunet, 2012). Additionally, increased fidelity of protein synthesis, which can be influenced by lysine residues in ribosomal proteins, has been linked to extended lifespan in various organisms (Martinez-Miguel et al., 2021). While specific effect sizes for lysine alone are not provided, these studies suggest that lysine supplementation may contribute to longevity through multiple mechanisms, including protein metabolism and epigenetic regulation.
 
Magnesium citrate anhydrous
Magnesium citrate anhydrous is considered a longevity compound due to its superior bioavailability compared to other forms like magnesium oxide (Kappeler et al., 2017). Magnesium plays a crucial role in various physiological processes and is linked to all hallmarks of aging (Dominguez et al., 2024). Chronic magnesium deficiency, common in older adults, leads to oxidative stress and low-grade inflammation, contributing to age-related diseases (Barbagallo & Dominguez, 2018). Dietary magnesium supplementation has shown promising results in extending lifespan and improving metabolic health in animal models (Fan et al., 2021; Villa-Bellosta, 2020). Magnesium acts as an antioxidant, protects mitochondria, and may help maintain telomere length (Barbagallo & Dominguez, 2010; Rowe, 2012). While specific effect sizes on longevity outcomes in humans are not provided, maintaining optimal magnesium balance throughout life may contribute to healthy aging and potentially extend healthspan (Deledda et al., 2022).
 
Vitamin B6 (Pyridoxine HCL)
Vitamin B6 is a versatile compound involved in numerous biochemical reactions and cellular processes, making it potentially beneficial for longevity (Mooney et al., 2009; Hellmann & Mooney, 2010). It functions as an enzymatic cofactor and a potent antioxidant, rivaling carotenoids and tocopherols in quenching reactive oxygen species (Mooney et al., 2009; Stach et al., 2021). Vitamin B6 supplementation has been shown to reduce core body temperature in rats, possibly indicating decreased metabolic rate, which may have implications for aging research (Lindseth & Hicks, 1982). While direct evidence for cognitive benefits in humans is limited (Malouf & Evans, 2003; Malouf & Grimley Evans, 2003), vitamin B6 is involved in homocysteine metabolism, and deficiency is associated with elevated homocysteine levels, a risk factor for cardiovascular disease and potentially Alzheimer's disease (Spinneker et al., 2007). Further research is needed to fully elucidate the potential longevity benefits of vitamin B6 supplementation in humans.
 
Vitamin D3 (VegD3)
Vitamin D3 has emerged as a potential longevity compound, with studies demonstrating its ability to extend lifespan in model organisms. In C. elegans, vitamin D3 supplementation increased lifespan by up to 39% (Messing et al., 2013) and promoted protein homeostasis (Mark et al., 2016). Similar effects were observed in Drosophila, although the benefits were diet-dependent (Jin et al., 2024). Vitamin D3's longevity-promoting effects are attributed to its role in regulating stress response pathways, innate immunity, and metabolism (Huggins & Farris, 2022; Mark et al., 2016). In humans, vitamin D deficiency is associated with age-related diseases and increased mortality risk (Pérez-López et al., 2011). Vitamin D supplementation may improve immunocompetence and promote healthy aging by modulating the epigenome and transcriptome of immune cells (Carlberg & Velleuer, 2024). Large-scale clinical trials are underway to investigate vitamin D's potential to reduce all-cause mortality (Garay, 2021), which could provide definitive evidence for its role as a longevity compound.
 
Vitamin K2 (MK4 and MK7)
Vitamin K2, particularly menaquinone-7 (MK-7), is considered a longevity compound due to its beneficial effects on bone and cardiovascular health. MK-7 has superior bioavailability and a longer half-life compared to other vitamin K forms (Schurgers et al., 2007). It promotes bone quality and strength by enhancing osteocalcin carboxylation and collagen production (Sato et al., 2020; Sato, 2013). MK-7 supplementation has been shown to reduce fracture risk and improve bone mineral density (Capozzi et al., 2019). In cardiovascular health, MK-7 activates matrix Gla protein, inhibiting arterial calcification (Sato, 2013). Vitamin K2 also demonstrates potential in improving insulin sensitivity, enhancing fat metabolism, and extending lifespan in C. elegans (Qu et al., 2022). Additionally, it exhibits anti-inflammatory properties and may have beneficial effects on diabetes, cancer, and neurodegenerative diseases (Jadhav et al., 2022). These diverse health benefits contribute to vitamin K2's reputation as a longevity compound (Halder et al., 2019).
 
Lithium (as Lithium Orotate)
Lithium has emerged as a promising longevity compound, with studies demonstrating its life-extending effects in various organisms. In Drosophila, lithium extended lifespan by inhibiting GSK-3 and activating NRF-2 (Castillo-Quan et al., 2016). Human studies using UK Biobank data revealed decreased mortality in lithium-treated individuals with affective disorders (Araldi et al., 2023). Lithium orotate may offer superior efficacy and reduced toxicity compared to lithium carbonate (Pacholko & Bekar, 2021). Chronic lithium use in bipolar disorder patients was associated with longer telomeres (Coutts et al., 2018). Low-dose lithium exposure in drinking water correlated with decreased all-cause mortality in a Japanese cohort (Zarse et al., 2011). In C. elegans, lithium extended lifespan by up to 46% through altered expression of nucleosome-associated genes (McColl et al., 2008). Lithium's anti-aging effects in bipolar disorder include reduced oxidative stress and slowed epigenetic aging (Salarda et al., 2021).
 
Boron (as Boron Glycinate)
Boron, particularly as boron glycinate, is emerging as a potential longevity compound due to its various beneficial effects. It has been shown to influence NAD+ and SAM formation and activity, which are known to affect aging and longevity (Nielsen, 2018). Boron exhibits antioxidant and anti-inflammatory properties, potentially reducing cardiovascular disease risk factors (Donoiu et al., 2018). When combined with stevia, boron may enhance longevity through anti-glycation effects (Scorei & Dinca, 2015). Glycine, a component of boron glycinate, has been found to extend lifespan in C. elegans by 21.6% through the methionine cycle (Liu et al., 2018). Recent research suggests that nicotinamide riboside borate, a more stable form of NR, may offer advantages in NAD+ supplementation for healthy aging (Biță et al., 2023). While direct evidence of boron's impact on human longevity is limited, its potential to modulate various age-related pathways warrants further investigation.
 
Copper
Copper plays a complex role in longevity and aging. While high concentrations can induce premature senescence in human fibroblasts (Matos et al., 2012), low doses of copper compounds combined with gluconic acid increased Drosophila lifespan by 21.6% (Massie et al., 1984). Copper's dual effect is evident in its involvement in reactive oxygen species (ROS) generation as a cofactor in the respiratory chain, while also being essential for ROS-scavenging enzymes like Cu/Zn superoxide dismutase (Stumpferl et al., 2004). A pro-oxidant combination of resveratrol and copper reduced multiple biological hallmarks of aging in mice, including telomere attrition and DNA damage (Pal et al., 2022). Copper's role in cell death and autophagy regulation has implications for cancer treatment (Xue et al., 2023). However, normal levels of copper may contribute to age-related diseases like atherosclerosis and Alzheimer's (Brewer, 2007). Copper compounds show potential as anticancer agents through oxidative stress induction and proteasome inhibition (Daniel et al., 2007; Tardito & Marchiò, 2009).
 
Sodium hyaluronate (Hyaluronic acid)
Sodium hyaluronate, or hyaluronic acid (HA), is considered a longevity compound due to its diverse biological effects. High molecular weight HA contributes to cancer resistance and longevity in naked mole rats, extending their lifespan to 32 years compared to 4 years in mice (Fisher, 2015). Transgenic mice overexpressing naked mole rat HAS2 showed lower cancer incidence, extended lifespan, and improved healthspan (Zhang et al., 2022). In C. elegans, sodium hyaluronate treatment increased lifespan by 0.27-fold and improved antioxidant enzyme activity (Lin et al., 2023). HA demonstrates anti-aging properties in skin rejuvenation, improving hydration, collagen stimulation, and reducing wrinkles (Bukhari et al., 2018). Its safety profile in cosmetic applications has been well-established (Becker et al., 2009). The molecular weight of HA is crucial, with high molecular weight HA associated with protective effects and longevity (Bohaumilitzky et al., 2017; Tian et al., 2013).
 
Vitamin K1
Vitamin K, particularly K2, is emerging as a potential longevity compound due to its diverse roles beyond blood coagulation. It acts as a cofactor for γ-glutamyl carboxylase, activating proteins involved in calcium homeostasis, bone mineralization, and vascular health (Azuma & Inoue, 2019; Mahajan & Katoch, 2022). Vitamin K has shown promise in preventing age-related diseases such as osteoporosis, cardiovascular disease, and cognitive decline (Popa et al., 2021). It also exhibits anti-inflammatory and antioxidant properties (Harshman & Shea, 2016; Simes et al., 2020). While both K1 and K2 are beneficial, K2 (especially MK-7) demonstrates superior absorption, tissue distribution, and bioavailability (Halder et al., 2019). K2 has been associated with regulating osteoporosis, atherosclerosis, cancer, and inflammatory diseases without adverse effects (Halder et al., 2019). However, more research is needed to establish definitive effect sizes and recommend specific dietary intakes for K2 (Mladěnka et al., 2021; Akbulut et al., 2020).
 
Manganese (as Manganese Citrate)
Manganese (Mn) is an essential metal that plays a crucial role in antioxidant defense mechanisms and longevity. Studies have shown that Mn-superoxide dismutase (MnSOD) gene variants are associated with increased longevity and decreased mortality in the oldest old (Soerensen et al., 2009). Low-dose Mn supplementation has demonstrated protective effects against oxidative stress and neurodegeneration in animal models (Sziráki et al., 1995; Bonilla et al., 2012). In human fibroblasts, Mn supplementation increases SOD2 activity and reduces superoxide anion generation in senescent cells (Ghneim, 2016). However, excessive Mn exposure can lead to neurotoxicity and oxidative damage (Parmalee & Aschner, 2016; Michalke, 2016). The antioxidant L-cysteine has shown potential in mitigating Mn-induced oxidative stress (Liapi et al., 2008). Interestingly, MnSOD may regulate longevity not solely through its antioxidant function but also by modulating physiological redox signaling (Honda et al., 2010).