Top 10 Longevity Ingredients Favored by Biohackers: A Comprehensive Guide

In an era of rapid anti-aging advancements, biohackers worldwide are pushing the boundaries of healthspan through targeted supplementation. Below are the top 10 longevity ingredients that have become "anti-aging staples" among global enthusiasts, backed by robust scientific mechanisms, conclusive clinical data, and the ability to slow aging at the cellular level—even reverse biological age.

1. Spermidine

Core Mechanisms & Benefits

As a natural polyamine, spermidine’s primary anti-aging action is potently activating autophagy—acting like "cellular janitors" to clear damaged proteins and senescent organelles. It also regulates the mTOR signaling pathway, preserves telomere length, boosts nitric oxide bioavailability, and reduces oxidative stress, comprehensively targeting key hallmarks of aging such as genomic instability and cellular senescence.

Clinical Data

• Animal Studies: A 2016 Nature Medicine study confirmed spermidine supplementation extends lifespan in mice, reduces cardiac hypertrophy, and improves diastolic function. A 2017 Cell Death & Disease study showed it mitigates high-calorie diet-induced weight gain and lowers obesity-related symptom rates in mice. A 2013 Mechanisms of Ageing and Development study found spermidine reverses arterial aging and alleviates endothelial cell oxidative damage in mice.
  
• Human Clinical Trials: The Bruneck Cohort Study demonstrated that dietary spermidine intake significantly improves blood pressure, reducing cardiovascular disease incidence by over 30% and mortality by 25%. A 2012 large-scale epidemiological study across 48 countries revealed a strong negative correlation between dietary polyamine levels and cardiovascular disease mortality.

Notable Advocates

• Daniel Lewis (35-year-old attorney), current leader of the Rejuvenation Olympics, includes spermidine in his core anti-aging regimen. When combined with AKG and NAD+ precursors, it helps him maintain a physiological state far beyond his peers, with an aging rate significantly slower than average.
• Spermidine is widely regarded as a "daily essential supplement" in the global biohacking community, valued for its irreplaceable role in cardiovascular protection and cancer prevention.

2. NAD+: NMN & NR

Core Mechanisms & Benefits

NAD+ (nicotinamide adenine dinucleotide) is a critical coenzyme for cellular energy metabolism, and its levels decline steadily with age. NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside)—direct NAD+ precursors—rapidly penetrate cell membranes to boost intracellular NAD+ levels. This activates the SIRT1-7 sirtuin family (longevity genes), enhances DNA repair capacity, preserves telomere length, and improves mitochondrial function, slowing cellular aging at its root. While their core benefits overlap, research shows NMN excels in improving energy metabolism and physical activity, while NR offers unique advantages in neuroprotection and cognitive function enhancement.

Clinical Data

• Animal Studies: Research led by Dr. Shin-ichiro Imai’s team at the University of Washington found that injecting elderly mice with eNAMPT (an enzyme that promotes NAD+ synthesis) from young mice extended their maximum lifespan to 1,029 days (≈2.8 years)—far exceeding the control group’s 881 days (≈2.4 years). The treated mice also showed significant improvements in motor vitality, sleep quality, and cognitive function.
• Human Clinical Trials: Healthy adults supplementing with 1,000mg of NMN daily saw a 40%+ increase in NAD+ levels in peripheral blood mononuclear cells after 4 weeks. Elderly individuals taking 500mg of NR daily for 12 weeks experienced a 12% boost in muscle strength and a 15% improvement in insulin sensitivity.

Notable Advocates

• Bryan Johnson, Silicon Valley billionaire and founder of the "Blueprint Program," lists NMN/NR as core supplements. Despite spending $2 million annually on his anti-aging regimen, he consistently ranks 5th–6th in the Rejuvenation Olympics.
• Julie Gibson Clark (55-year-old mother of two), current Rejuvenation Olympics champion, spends just $108 per month on supplements—with NR as a key component. Her biological age is only 36, and her aging rate is 0.665x that of the average person.

3. Ergothioneine

Core Mechanisms & Benefits

As the only natural antioxidant capable of penetrating mitochondrial membranes, ergothioneine selectively neutralizes 80% of mitochondrial free radicals. It inhibits the NF-κB inflammatory pathway and NLRP3 inflammasome activation, reducing oxidative damage and chronic inflammation at the source. Additionally, it activates cellular antioxidant defense systems, protects DNA and mitochondrial integrity, and promotes collagen synthesis—delivering both internal and skin-focused anti-aging benefits.

Clinical Data

• Animal Studies: Mouse experiments showed ergothioneine supplementation reduces UV-induced skin aging damage by 40%, decreases mitochondrial damage in nerve cells by 35%, and slows cognitive decline by 28%.
• Human Clinical Trials: A 12-week clinical trial by Kyoto University (Japan) found that daily supplementation with 15mg of ergothioneine—when combined with PQQ—increased collagen density in the skin’s dermis by 22% and reduced serum levels of the inflammatory cytokine IL-6 by 18%. Highly active ergothioneine extracted from French black truffles was shown to soften nasolabial folds and enhance jawline definition within 4 weeks.

Notable Advocates

• Dave (62-year-old biohacker), who takes 170 supplements daily, cites ergothioneine as his core antioxidant. It helps him maintain healthy telomere length and avoid age-related macular degeneration—a condition he was genetically predisposed to.
• The "ergothioneine + PQQ" synergistic stack is widely popular in anti-aging circles, hailed as the "gold standard for mitochondrial protection" and endorsed by leading health optimization experts like Siim Land.

4. AKG (Alpha-Ketoglutarate)

Core Mechanisms & Benefits

A key intermediate in the tricarboxylic acid cycle, AKG’s core mechanism is regulating epigenetic modifications—activating cellular TET enzyme function to clear harmful DNA methylation. It also supplements substrates for cellular energy metabolism, maintains mitochondrial function, promotes collagen synthesis, increases bone density, and improves gut health—supporting both internal function and external vitality.

Clinical Data

• Animal Studies: Elderly rats supplemented with Ca-AKG (calcium alpha-ketoglutarate) for 6 months showed an 18% increase in bone density, a 22% reduction in muscle loss, and a 12–15% extension in lifespan.
• Human Clinical Trials: Research from the National University of Singapore demonstrated that continuous supplementation with Ca-AKG for 7 months reduced participants’ average biological age by 8 years. Daily intake of 1,000mg of Ca-AKG improved cognitive function scores in the elderly by 25% and sleep quality by 30%.

Notable Advocates

• Rejuvenation Olympics champion Daniel Lewis takes 600mg of liposomal Ca-AKG daily, calling it "the key to reversing the epigenetic clock" and crediting it with maintaining his top-tier physiological condition.
• Dr. Brian Kennedy—known as the "Father of AKG" and a core member of the team that discovered sirtuins—leads AKG anti-aging research, serves as a scientific advisor for related brands, and personally endorses its efficacy.

5. Akkermansia muciniphila

Core Mechanisms & Benefits

A key gut probiotic, Akkermansia’s anti-aging effects stem from regulating gut microbiota balance, repairing the intestinal mucosal barrier, and reducing intestinal inflammatory leakage. Its secreted Amuc_1100 protein improves insulin sensitivity, regulates lipid metabolism, and influences immune function and brain health via the gut-brain axis—indirectly targeting aging hallmarks like chronic inflammation and dysbiosis.

Clinical Data

• Animal Studies: Obese mice supplemented with Akkermansia showed a 12% reduction in body weight, a 30% improvement in insulin resistance, and a 25% decrease in liver fat accumulation after 8 weeks.
• Human Clinical Trials: The first human trial (2019, Nature Medicine) found that daily intake of 10 billion TFU of inactivated Akkermansia improved insulin sensitivity by 28.6% (P=0.002) and reduced total cholesterol by 8.7% (P=0.02) after 3 months. A 2025 double-blind, placebo-controlled trial (160 participants)—the largest to date—confirmed that 90 days of daily supplementation with 34 billion TFU of Akkermansia reduced average total cholesterol by 0.48 mmol/L, body weight by 1.42 kg, and waist circumference by 3.58 cm.

Notable Advocates

• Akkermansia is ranked the "top gut anti-aging supplement" by the global biohacking community, particularly popular among metabolic optimization enthusiasts.
• Anti-aging expert Siim Land highlights Akkermansia in his metabolic health protocols, describing it as "the critical link between gut health and systemic anti-aging."

6. Metformin

Core Mechanisms & Benefits

A classic anti-diabetic drug, metformin acts as an "affordable anti-aging powerhouse" by activating the AMPK signaling pathway, inhibiting mTOR, and boosting autophagy. It also improves insulin resistance, reduces chronic inflammation, and lowers oxidative stress—slowing cellular aging and targeting key aging hallmarks like deregulated nutrient sensing and chronic inflammation.

Clinical Data

• Animal Studies: Middle-aged mice supplemented with metformin (150mg/kg daily) showed an 18% extension in lifespan, a 40% reduction in tumor incidence, and a 35% decrease in cardiovascular disease risk.
• Human Clinical Trials: A 10-year follow-up study of adults over 65 found that daily intake of 1,500mg of metformin reduced all-cause mortality by 25% and the incidence of age-related diseases (diabetes, cardiovascular disease) by 30%. Dr. Zhan, a reproductive medicine specialist who has taken metformin for 7 years, maintains youthful insulin sensitivity and shows no significant signs of aging in routine checkups.

Notable Advocates

• Dr. Zhan (56-year-old clinical physician) takes 1,500mg of metformin daily alongside 30+ other supplements. After 7 years, his physiological condition far exceeds that of his peers, making him a poster child for "evidence-based anti-aging."
• Silicon Valley billionaire Bryan Johnson includes metformin in his Blueprint Program as a core metabolic regulator, helping him maintain an extremely slow aging rate.

7. PQQ (Pyrroloquinoline Quinone)

Core Mechanisms & Benefits

Dubbed the "mitochondrial superactivator," PQQ’s core mechanism is stimulating mitochondrial biogenesis, boosting ATP production efficiency, and enhancing mitochondrial function. It also activates the SIRT1 longevity gene, promotes neurotrophic factor secretion, and protects the nervous system. When combined with ergothioneine, it forms a synergistic "energy activation + oxidative protection" anti-aging stack.

Clinical Data

• Animal Studies: Elderly mice supplemented with PQQ (20mg/kg daily) for 8 weeks showed a 40% increase in mitochondrial count, a 50% boost in exercise endurance, and a 35% improvement in hippocampal neuronal plasticity.
• Human Clinical Trials: A long-term study of 8,620 middle-aged and elderly adults found that daily supplementation with 20mg of PQQ improved memory by 22% and increased average hippocampal volume by 2.8% (via MRI) after 12 weeks. When taken with ergothioneine, it enhanced cellular antioxidant enzyme activity by 40% and reduced mitochondrial damage by 35%.

Notable Advocates

• Pavel (32-year-old Russian biohacker) includes PQQ in his "human optimization protocol," combining it with light therapy and cold exposure. His VO2 max rivals that of Olympic athletes, and his biological age is 12 years younger than his chronological age.
• Josh Best (health optimization expert, 6th place in the Rejuvenation Olympics) cites PQQ as his core neuroprotective supplement, calling it "the key to boosting mental and physical performance."

8. Vitamin D

Core Mechanisms & Benefits

By binding to intracellular vitamin D receptors (VDR), vitamin D regulates the expression of thousands of genes. Its core anti-aging mechanism is preserving telomere length and slowing telomere shortening. It also modulates immune function, reduces chronic inflammation, improves calcium metabolism and bone health, and lowers the risk of age-related diseases (cancer, autoimmune disorders).

Clinical Data

• Animal Studies: Elderly mice supplemented with vitamin D3 (500 IU/kg daily) showed a 30% reduction in telomere shortening rate, a 28% decrease in tumor incidence, and a 15% increase in bone density.
• Human Clinical Trials: The VITAL randomized controlled trial (5-year follow-up, 1,054 participants) found that daily supplementation with 2,000 IU of vitamin D3 significantly slowed telomere shortening over 4 years—equivalent to delaying aging by nearly 3 years. It also reduced the risk of advanced cancer by 20% and autoimmune diseases by 18%.

Notable Advocates

• Clinical physician Dr. Zhan includes vitamin D3 in his daily foundational supplements, calling it "the most cost-effective anti-aging ingredient" for synergistically maintaining endocrine balance with other supplements.
• David Pascoe (61-year-old Rejuvenation Olympics participant, biological age 38) spends $200,000 annually on his anti-aging regimen, with vitamin D3 as a non-negotiable base. Combined with hyperbaric oxygen therapy, it helps him achieve profound age reversal.

9. Astaxanthin

Core Mechanisms & Benefits

A top-tier carotenoid with a unique structure of 13 conjugated double bonds, astaxanthin boasts extraordinary antioxidant capacity—550x that of vitamin E. It protects cell membrane lipids from oxidative damage, inhibits inflammatory cytokine release, and safeguards the cardiovascular system, retina, and nerve cells—targeting aging hallmarks like oxidative stress and chronic inflammation.

Clinical Data

• Animal Studies: Elderly rats supplemented with astaxanthin (10mg/kg daily) for 12 weeks showed a 40% reduction in myocardial infarction size, a 50% decrease in retinal oxidative damage, and a 30% improvement in cognitive function scores.
• Human Clinical Trials: Three Japanese randomized controlled trials confirmed that daily supplementation with 4–12mg of astaxanthin reduces age-related cognitive and memory impairments. A meta-analysis of 10 human trials found it significantly lowers thrombosis risk and reduces average blood pressure by 5–8mmHg.

Notable Advocates

• Dr. Bruce Ames (90-year-old U.S. National Academy of Sciences member), who published research on astaxanthin in Proceedings of the National Academy of Sciences, lists it as one of the top 10 "longevity nutrients" and takes it daily.
• The biohacking community widely favors natural astaxanthin for its irreplaceable "whole-body protection" properties, hailing it as an ideal ingredient for both internal health and skin anti-aging.

10. Urolithin A

Core Mechanisms & Benefits

A metabolite of ellagic acid produced by gut microbiota, urolithin A is a "cellular quality control enhancer" whose core anti-aging mechanism is activating mitophagy—clearing old, damaged mitochondria and promoting the generation of new ones. It also inhibits collagen-degrading enzyme (MMP-1), promotes collagen synthesis, and regulates gut microbiota balance—delivering synergistic anti-aging benefits for muscles, skin, and the cardiovascular system.

Clinical Data

• Animal Studies: In a mouse model of Alzheimer’s disease, oral urolithin A reduced neuroinflammation by 35% and improved cognitive function by 40%. Elderly mice supplemented with urolithin A showed a 25% reduction in muscle loss and a 30% boost in exercise endurance.
• Human Clinical Trials: A JAMA Network Open trial (66 adults aged 65–90) found that daily supplementation with 1,000mg of urolithin A significantly improved leg muscle fatigue resistance after 2 months. A Cell Reports Medicine study (88 adults aged 40–65) confirmed that 1,000mg daily increased leg muscle strength by 12.2%. Four months of intervention also led to a significant reduction in the C18:0/C24:0 ceramide ratio—a cardiovascular risk marker (P<0.01).

Notable Advocates

• Marc Deforest (anti-aging tech enthusiast, 8th place in the Rejuvenation Olympics) includes urolithin A in his muscle anti-aging protocol, calling it "the key to maintaining muscle function in middle age and beyond."
• Biohackers commonly pair urolithin A with NMN and spermidine to form a "energy metabolism + cellular cleansing" gold stack, with many reporting significant improvements in fatigue and athletic performance.

References

1. Liu S, et al. Urolithin A improves muscle function and reduces cardiovascular risk markers in older adults. JAMA Network Open, 2022.

2. Liu S, et al. Urolithin A modulates ceramide metabolism in elderly populations. iScience, 2025.

3. Le T.M., et al. Urolithin A protects against UV-induced skin aging via inhibiting MMP-1 and promoting collagen synthesis. Antioxidants, 2022.

4. Moussa M.R., et al. Urolithin A production correlates with reduced inflammation and colon polyp risk. Cancer Prevention Research, 2025.

5. Imai S, et al. Circulating eNAMPT from adipose tissue delays aging and extends lifespan in mice. Cell Metabolism, 2019.

6. Kennedy B, et al. α-Ketoglutarate improves cognitive function and reverses biological age in humans. Journal of Gerontology, 2025.

7. JoAnn Manson, et al. Vitamin D supplementation preserves telomere length in a randomized controlled trial. American Journal of Clinical Nutrition, 2025.

8. Bruckbauer A, et al. Spermidine improves cardiovascular health and extends lifespan. Nature Medicine, 2016.

9. Depommier C, et al. Supplementation with Akkermansia muciniphila improves metabolic health in overweight humans. Nature Medicine, 2019.

10. Park JS, et al. Astaxanthin reduces oxidative stress and inflammation in humans. Journal of Nutritional Biochemistry, 2010.

11. Kim H, et al. Synergistic effects of PQQ and ergothioneine on mitochondrial function. Nature Communications, 2023.

12. Evans M, et al. Metformin activates AMPK and extends healthspan in humans. Aging Cell, 2023.

13. Moussa M, et al. Urolithin A induces mitophagy and improves muscle function. Nature Metabolism, 2021.

14. Schaffer S, et al. Polyamines and cardiovascular disease risk: an epidemiological study. Global Health Science Journal, 2012.

15. Zhang H, et al. Akkermansia muciniphila reduces cholesterol levels in hypercholesterolemic patients. Journal of Clinical Lipidology, 2025.