The first studies showing that AKG might be able to both extend lifespan and delay the onset of age-related diseases were done on roundworms.[1] More recent studies in mice also showed an increase in both lifespan and healthspan with AKG supplementation.[2][3] AKG also slows down muscle loss, both as an amino acid precursor and through its interaction with protein receptors that can reduce muscle atrophy. Through epigenetic regulation, AKG decreased signs of age-related bone loss in mice. One study showed that AKG supplementation increased bone mass and accelerated bone regeneration in mice.[4] Its anti-inflammatory effects, antioxidant effects, and its role in the production of glutamate could lower the risk of neurodegenerative diseases.[5][6][7] Interestingly, in some studies done in fruit flies and mice, AKG only had an impact on the lifespan of females, although healthspan did seem to improve in both males and females.[8][2][9] These all point to a promising role in anti-aging for AKG in the future, but more clinical trials will need to be done before AKG can be recommended as an anti-aging supplement for humans.
References
- ^Chin RM, Fu X, Pai MY, Vergnes L, Hwang H, Deng G, Diep S, Lomenick B, Meli VS, Monsalve GC, Hu E, Whelan SA, Wang JX, Jung G, Solis GM, Fazlollahi F, Kaweeteerawat C, Quach A, Nili M, Krall AS, Godwin HA, Chang HR, Faull KF, Guo F, Jiang M, Trauger SA, Saghatelian A, Braas D, Christofk HR, Clarke CF, Teitell MA, Petrascheck M, Reue K, Jung ME, Frand AR, Huang JThe metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR.Nature.(2014-Jun-19)
- ^Azar Asadi Shahmirzadi, Daniel Edgar, Chen-Yu Liao, Yueh-Mei Hsu, Mark Lucanic, Arash Asadi Shahmirzadi, Christopher D Wiley, Garbo Gan, Dong Eun Kim, Herbert G Kasler, Chisaka Kuehnemann, Brian Kaplowitz, Dipa Bhaumik, Rebeccah R Riley, Brian K Kennedy, Gordon J LithgowAlpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging MiceCell Metab.(2020 Sep 1)
- ^Oleksandr Demidenko, Diogo Barardo, Valery Budovskii, Robb Finnemore, Francis R Palmer, Brian K Kennedy, Yelena V BudovskayaRejuvant®, 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 testAging (Albany NY).(2021 Nov 30)
- ^Yuan Wang, Peng Deng, Yuting Liu, Yunshu Wu, Yaqian Chen, Yuchen Guo, Shiwen Zhang, Xiaofei Zheng, Liyan Zhou, Weiqing Liu, Qiwen Li, Weimin Lin, Xingying Qi, Guomin Ou, Cunyu Wang, Quan YuanAlpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylationsNat Commun.(2020 Nov 5)
- ^Gyanwali B, Lim ZX, Soh J, Lim C, Guan SP, Goh J, Maier AB, Kennedy BKAlpha-Ketoglutarate dietary supplementation to improve health in humans.Trends Endocrinol Metab.(2022-Feb)
- ^Naeini SH, Mavaddatiyan L, Kalkhoran ZR, Taherkhani S, Talkhabi MAlpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives.Exp Gerontol.(2023-May)
- ^Morita M, Kudo K, Shima H, Tanuma NDietary intervention as a therapeutic for cancer.Cancer Sci.(2021-Feb)
- ^Bayliak MM, Lushchak VIPleiotropic effects of alpha-ketoglutarate as a potential anti-ageing agent.Ageing Res Rev.(2021-Mar)
- ^Yuan Su, Tao Wang, Nan Wu, Diyan Li, Xiaolan Fan, Zhongxian Xu, Shailendra Kumar Mishra, Mingyao YangAlpha-ketoglutarate extends Drosophila lifespan by inhibiting mTOR and activating AMPKAging (Albany NY).(2019 Jun 26)