Longevity Supplements – 5 to Track & Consider

Taurine

Taurine is an amino acid found in various tissues in the body. Unlike most other amino acids, taurine is not used to build proteins. Still, it is vital for many health aspects and processes, including bile salt formation, cardiovascular function, eye health, central nervous system function, and skeletal muscle development.

Supplementation with taurine can significantly extend the lifespan of mice by 10-12%.¹Taurine deficiency as a driver of aging | Singh, P. et al. | 2023 | Science More importantly, it improves various markers of health in mice. That’s important because alongside extending lifespan, longevity research aims to support healthspan – the period of life spent in good health and free from chronic diseases.

One of the ways that taurine contributes to a longer lifespan and healthspan is by protecting against cardiovascular issues. That’s because it could lower blood pressure and improve vascular function in prehypertensive individuals, supporting cardiovascular health.²Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension | Sun, Q. et al. | 2016 | Hypertension

In addition, taurine possesses potent antioxidant and anti-inflammatory properties, which combat oxidative stress and inflammation. These two processes are involved with aging and the development of chronic diseases.

Dosage: The mouse longevity study used doses of 500-1000mg/kg/day. That would be equivalent to 3g-6.5g of taurine per day for humans. However, keep in mind that most human studies use doses of 1.5g-6g per day.

See here for Bryan Johnson’s current daily Taurine dose.

Examples of Taurine brands include:

Capsules

• NOW – Taurine – 1,000 mg – x100 veg capsules
• Life Extension – Taurine – 1,000 mg – x90 veg capsules

Powders

• NOW – Taurine – 8 oz (227g) powder
• Life Extension – Taurine – 10.6oz (300g) powder

Calcium Alpha-ketoglutarate (Ca-AKG)

Alpha-ketoglutarate (AKG) is a key intermediate compound in the citric acid cycle that our body uses to break down nutrients into energy.

AKG is not an essential nutrient, meaning our body can produce it. However, research suggests that its levels significantly decline with age, showing a 10-fold decrease from age 40 to 80.³Alpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives | Naeini, S.H. et al. | 2023 | Experimental Gerontology

This decline is important because AKG is not a compound we typically obtain directly from our diet. Instead, we can supplement it, and Ca-AKG appears to be the best form.

Studies on model organisms like Caenorhabditis elegans have shown that AKG supplementation can extend lifespan by up to 50%.⁴The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR | Chin, R.M. et al. | 2014 | Nature These benefits come from inhibiting ATP synthase, which leads to reduced ATP content, decreased oxygen consumption, and increased autophagy.

All of these effects are also the consequence of caloric restriction, and researchers believe that Ca-AKG boosts lifespan by mimicking caloric restriction and stimulating moderate reactive oxygen species (ROS) production in mitochondria.⁵Mimicking caloric restriction for anti-aging effects: The pro-oxidant role of alpha-ketoglutarate | Bayliak, M.M. et al. | 2022 | Comparative Toxicology and Pharmacology This activates the body’s natural defense mechanisms, which contributes to longevity.

Adding Ca-AKG to the diet of mice extended the relative lifespan of female mice by 10% and male mice by 5%. This supplementation was also associated with a decrease in systemic inflammatory cytokines, indicating a lower inflammation in the body, which is essential for extending the healthspan.⁶Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice | Shahmirzadi, A.A. et al. | 2020 | Cell Metabolism

Dosage: There is no established optimal dose for Ca-AKG. A small human study successfully used 1g of Ca-AKG two times per day.

See here for Bryan Johnson’s current daily Ca-AKG dose.

Examples of Ca-AKG brands include:

• Double Wood – Ca-AKG – 500 mg * 180 capsules (see 15% off coupon code)
• DoNotAge – Ca-AKG – 400 mg * 60 or 360 capsules (can ship from within EU) – 10% off with this discount code
• vitalityPro – Ca-AKG – 500 mg * 120 or 240 capsules (ships from UK)

Glycine

Glycine is a non-essential amino acid involved in various metabolic pathways and antioxidant processes. It appears to influence longevity by interacting with methionine, which is another amino acid.

Research on rodents provides compelling evidence of the longevity benefits of methionine restriction, with diets low in this amino acid extending lifespan by up to 45%.⁷Extension of Cellular Lifespan by Methionine Restriction Involves Alterations in Central Carbon Metabolism and Is Mitophagy-Dependent | Plummer, J.D. et al. | 2019 | Frontiers in Cell and Developmental Biology

Glycine is the sole acceptor of methyl groups from glycine-N-methyl transferase (GNMT), which is essential for methionine clearance. Supplementing with this amino acid could mimic the benefits of a low methionine diet by reducing methionine levels when consumed in excess⁸Glycine N-Methyltransferase and Regulation of S-Adenosylmethionine Levels | Luka, Z. et al. | 2009 | Journal of Biological Chemistry.

Research shows that glycine supplementation prolongs lifespan by 33.3% and mitigates aging-related gene expression changes in roundworms (Caenorhabditis elegans), promoting longevity through its role in methionine clearance.⁹Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion | Liu, Y.J. et al. | 2019 | PLOS Genetics

Adding glycine to the diet of mice increased lifespan by 4-6%.¹⁰Glycine supplementation extends lifespan of male and female mice | Miller, R.A. et al. | 2019 | Aging Cell In addition, researchers explored the effects of GlyNAC (glycine and N-Acetylcysteine), and the results were even stronger.

NAC serves as a precursor to glutathione, a powerful antioxidant that helps neutralize free radicals that damage cells and tissues in the body. Interestingly, supplementation with NAC has increased lifespan in studies with roundworms, fruit flies, and mice. ¹¹Compounds that extend longevity are protective in neurodegenerative diseases and provide a novel treatment strategy for these devastating disorders | Soo, S.K. et al. | 2020 | Mechanisms of Ageing and Development

GlyNAC supplementation increased mice’s lifespan by 24% and improved several aging-related factors.¹²GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage | Kumar, P. et al. | 2022 | Nutrients

Dosage: The optimal glycine dosage protocol hasn’t been established. Clinical trials used doses of 1g to 15g per day depending on the desired outcome. A recent study suggested that 100mg/kg/day is a safe and well-tolerated dose in the context of longevity. That would translate to 8g of glycine for an 82kg (180lbs) person (the size of dose might want to take via powder rather than capsules).

Examples of Glycine brands include:

• Life Extension – Glycine – 1,000 mg capsules (see 20% off coupon code)
• NOW – Glycine – 1,000 mg capsules (see 20% off coupon code)

Creatine

Athletes and fitness enthusiasts widely use creatine to increase strength and boost muscle growth and recovery. It appears that the impact of creatine can also extend beyond the gym.

Current research suggests that creatine has significant neuroprotective benefits, which can extend lifespan in animal models. For example, one study showed that creatine supplementation was linked to a 9% increase in the median lifespan in aging mice.¹³Creatine in mouse models of neurodegeneration and aging | Klopstock, T. et al. | 2011 | Amino Acids

In addition, creatine supplementation contributed to better neurobehavioral performance and a reduction in markers of aging, such as reactive oxygen species levels and lipofuscin accumulation in the brain.

Despite promising results in animal studies, the results of human clinical trials, particularly for neurodegenerative diseases like Parkinson’s and Huntington’s, have been mixed. We need more clinical trials to determine whether creatine has the same longevity benefits in humans.

What we do know is that creatine can improve lean muscle mass, muscle function, and possibly cognitive processing and bone health, even at old age.¹⁴Creatine supplementation in the aging population: effects on skeletal muscle, bone, and brain | Gualano, B. et al. | 2016 | Amino Acids However, supplementation with creatine has been studied more extensively in young, healthy adults (mostly athletes), and similar benefits have been observed. This highlights the potential of creatine to support health and longevity throughout different life stages, regardless of protein intake.

Dosage: There is no established creatine dose for longevity. According to that longevity study in mice, some human studies use a dose of 10g/day. However, that may seem excessive considering that most longevity enthusiasts consume 3-5g of creatine per day.

Reputable brands of creatine powder include:

Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR)

Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are critical precursors to nicotinamide adenine dinucleotide (NAD) – a molecule that’s vital for DNA repair, energy metabolism, gene expression, and cellular signaling.

NAD levels naturally decline with age, and it is speculated that this plays a role in the aging process. So, the idea behind supplementing with NMN and NR is to boost NAD levels and contribute to healthy aging.

Although NR and NMN are effective at increasing NAD levels, there isn’t evidence that NAD boosters increase lifespan. For example, a 2021 ITP trial found no effects of NR on longevity.¹⁵17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex | Harrison, D.E. et al. | 2021 | Aging Cell

Despite the mixed results regarding lifespan extension, NMN and NR have shown promise in enhancing healthspan. Research has demonstrated that NMN supplementation can reverse age-related arterial dysfunction and oxidative stress in mice, improving cardiovascular health.¹⁶Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice | de Picciotto, NE et al. | 2016 | Aging Cell

Similarly, NR has been found to protect against muscle function decline and stem cell loss, pointing towards significant improvements in healthspan and potentially delaying the onset of age-related diseases.¹⁷NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice | Zhang, H. et al. | 2016 | Science

Dosage: Most studies use doses of 100-1000mg of NMN/NR per day. However, the optimal dosage protocol hasn’t been established yet.

It may also vary by individual depending on their baseline NAD level and their desired level.

Examples of NMN brands include:

• Renue – NMN powder – 100 grams total (use 10% off use coupon code)
• Renue – NMN – 125 mg x 240 capsules (use 10% off use coupon code)
• Super NMN – 500 mg x 90 capsules

Examples of NR brands include:

• Niagen – NR – 500 mg x 60 capsules
• ProHealth – NR – 500 mg x 60 capsules
• Renue – NR (Liposomal) – 300 mg x 90 capsules