Calcium alpha-ketoglutarate extended lifespan of mice in recent study

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A recent study published in Cell Metabolism¹ found that mice fed chow supplemented with calcium alpha-ketoglutarate (Ca-aKG) saw extended lifespans. Ca-aKG is a key metabolite in the tricarboxylic acid cycle, which is a series of reactions vital for oxygen-dependent derivation, and as the alpha-keto acid of glutamate, Ca-aKG is also an important component of amino acid metabolism.

In the study, mice were initially fed regular mouse chow, but then at middle age (18 months), mice were fed that same chow with Ca-aKG. Researchers evaluated two cohorts of mice (182 total) to assess the reproducibility of the longevity effects. Results showed that supplementation with Ca-aKG significantly improved median lifespan and survival (age at 90th percentile mortality), but this effect was sexually dimorphic, favoring females. Specifically, in the first cohort of females, median lifespan and survival significantly increased by 16.6% and 19.7%, respectively. In the second cohort of females, median lifespan and survival were significantly increased by 10.5% and 8%, respectively. In males, median lifespan increased by 9.6% and 12.8% in each cohort. Survival increased in males, but it was not found to be statistically significant in either cohort.

The mice also saw significantly decreased proportion of life in which they were frail. Frailty scores were reduced by 46% for females and 41% for males. The severity of age-dependent phenotypes was also decreased. Females saw a significant decrease in fur color loss, piloerection, poor coat condition, dermatitis, gait disorder, and kyphosis. Males saw a decrease in severity of body condition, dermatitis, gait disorder, eye discharge, kyphosis, and tumors. Not all phenotypes improved. For example, treated mice did not perform better in treadmill exhaustion tests, and showed no improvements in cardiac function. However, no significant adverse changes were detected with Ca-aKG treatment.

Ca-aKG is sold as LifeAKG, a pure, patent-pending, sustained release form that can be found in Rejuvant LifeTabs, sold by Ponce De Leon Health Inc. (Fernandina Beach, FL). While more research is necessary to draw any conclusions about the effects of Ca-aKG in humans, this new study places a renewed emphasis on the role of metabolism in aging biology.

Reference

1. Shahmirzadi AA et al. “Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice.” Cell Metabolism, vol. 32, no. 3 (2020): 447-45