Train Harder and Age Slower: The AKG Breakthrough That's Revolutionizing Performance and Longevity

As someone who has dedicated decades to optimizing human performance and extending healthy lifespan, I'm constantly seeking evidence-based interventions that deliver measurable results. Today, I want to share groundbreaking research on Alpha-Ketoglutarate (AKG) that demonstrates how this naturally occurring metabolite is simultaneously enhancing athletic performance and reversing biological aging.

The Science Spotlight

Your weekly deep dive into breakthrough research

Revolutionary Longevity Research

A landmark study published in Cell Metabolism by researchers at the Buck Institute for Research on Aging has fundamentally changed our understanding of AKG's anti-aging potential.¹ Scientists fed middle-aged mice (equivalent to 55-year-old humans) a diet containing calcium alpha-ketoglutarate (Ca-AKG) and observed remarkable results:

• Female mice lived 8-20% longer after starting AKG supplementation

• Frailty scores improved by over 40% across 31 physiological measurements including hair color, hearing, walking gait, and grip strength

• Chronic inflammation decreased significantly through increased IL-10 production

• Healthspan extended dramatically - mice stayed healthier longer, compressing the period of age-related decline

The researchers discovered that AKG works by inhibiting the mTOR pathway while activating AMPK signaling - the same pathways activated by caloric restriction and exercise. This creates what scientists call "compressed morbidity" - living longer while staying healthier.

The Cellular Energy Connection

What makes this research credible is AKG's fundamental role in cellular metabolism. As a key intermediate in the tricarboxylic acid (TCA) cycle, AKG is essential for energy production in every cell. However, AKG levels decline dramatically between ages 40-80, correlating with decreased cellular function and increased aging.

Recent research published in Aging demonstrates that AKG acts as a cofactor for DNA demethylases - enzymes that can literally reverse epigenetic aging marks on our DNA.² This explains why AKG supplementation doesn't just slow aging; it can actually reverse biological age markers.

Exercise Performance Breakthrough

A controlled study published in Nutrition examined AKG's impact on trained athletes.³ Researchers found that L-arginine alpha-ketoglutarate (AAKG) supplementation significantly improved:

• One-repetition maximum bench press performance

• Wingate peak power output (measuring anaerobic capacity)

• Blood glucose regulation during exercise

The mechanism involves AKG's role in energy metabolism combined with improved blood flow through enhanced nitric oxide production. This dual action explains why AKG benefits both longevity and performance - optimizing cellular energy production while improving nutrient delivery to working muscles.

Real Results Radar

Evidence from the field

The 8-Year Age Reversal Study

The most compelling human evidence comes from a retrospective analysis of 42 individuals published in Aging.⁴ Participants took Rejuvant® (calcium alpha-ketoglutarate plus vitamins) for an average of 7 months. Using the TruAge DNA methylation test - a validated biomarker of biological aging - researchers documented extraordinary results:

• 40 out of 42 participants decreased their biological age

• Average biological age reduction: 8 years

• Most responsive participants: Those who were biologically older than their chronological age at baseline

• Duration: Results achieved in just 4-10 months of supplementation

To put this in perspective, previous lifestyle interventions like fasting and exercise typically reduce biological age by only 2 years after more than one year of consistent practice.

Clinical Performance Data

A double-blind, placebo-controlled study published in the International Journal of Sport Nutrition and Exercise Metabolism examined 35 trained men supplementing with creatine plus arginine alpha-ketoglutarate.⁵ Results showed:

• Bench press repetitions increased from 30.9 to 34.9 (13% improvement)

• Wingate peak power increased from 741W to 794W (7% improvement)

• No adverse effects reported during the 10-day supplementation period

Ongoing Clinical Validation

The ABLE (Alpha-ketoglutarate supplementation and BiologicaL agE) study currently underway at the National University of Singapore represents the gold standard for AKG research.⁶ This double-blind, placebo-controlled trial is testing 1g daily sustained-release Ca-AKG in 120 middle-aged adults over 6 months, measuring:

• DNA methylation age changes

• Handgrip and leg extension strength

• Arterial stiffness and cardiovascular markers

• Inflammatory biomarkers and metabolic parameters

These real-world results demonstrate that AKG isn't just promising in laboratory settings - it's delivering measurable benefits in human performance and longevity metrics that matter.

Ready to explore how AKG might fit into your optimization protocol? The intersection of enhanced performance and extended healthspan represents the future of human optimization. While we await additional clinical data, the current evidence suggests AKG deserves serious consideration in any evidence-based longevity and performance strategy.

Discover comprehensive AKG protocols, dosing strategies, and advanced implementation techniques in the Newsletter secton at  www.bioprecisionaging.com where average is not the target.

Scientific References

¹ Asadi Shahmirzadi A, Edgar D, Liao CY, et al. Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. Cell Metab. 2020;32(3):447-456.e6. PMID: 32877690

² Demidenko O, Barardo D, Budovskii V, et al. Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging (Albany NY). 2021;13(24):24485-24499. PMID: 34893602

³ Campbell B, Roberts M, Kerksick C, et al. Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men. Nutrition. 2006;22(9):872-81. PMID: 16928472

⁴ Demidenko O, Barardo D, Budovskii V, et al. Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging (Albany NY). 2021;13(24):24485-24499. PMID: 34893602

⁵ Little JP, Forbes SC, Candow DG, et al. Creatine, arginine α-ketoglutarate, amino acids, and medium-chain triglycerides and endurance and performance. Int J Sport Nutr Exerc Metab. 2008;18(5):493-508. PMID: 19033611

⁶ McGee KC, Sullivan J, Hazeldine J, et al. Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)-intervention study protocol. Geroscience. 2023;45(5):2897-2907. PMID: 37217632

The information provided in this post is for educational purposes only and is not intended as medical advice, diagnosis, or treatment. Please consult with your healthcare provider before starting any new supplement regimen, exercise program, or making significant changes to your health routine, especially if you have existing medical conditions or take medications.