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Alpha Ketoglutarate

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• α-ketoglutarate suppresses immediate early gene expression in cancer cells - Biochem Biophys Res Commun 2022 Nov 11 - "Cancer cells exhibit increased glutamine consumption compared to normal cells, supporting cell survival and proliferation. Glutamine is converted to α-ketoglutarate (αKG), which then enters the tricarboxylic acid cycle to generate ATP. Recently, therapeutic modulation of glutamine metabolism has become an attractive metabolic anti-cancer strategy ... Together, these findings indicate that therapeutic targeting of IEG dysregulation by αKG can be a potentially effective anti-cancer therapeutic strategy for glutamine metabolism inhibitors" - See alpha ketoglutarate at Amazon.com.
• Human age reversal: Fact or fiction? - Aging Cell 2022 Jul 2 - "Although chronological age correlates with various age-related diseases and conditions, it does not adequately reflect an individual's functional capacity, well-being, or mortality risk. In contrast, biological age provides information about overall health and indicates how rapidly or slowly a person is aging. Estimates of biological age are thought to be provided by aging clocks, which are computational models (e.g., elastic net) that use a set of inputs (e.g., DNA methylation sites) to make a prediction. In the past decade, aging clock studies have shown that several age-related diseases, social variables, and mental health conditions associate with an increase in predicted biological age relative to chronological age. This phenomenon of age acceleration is linked to a higher risk of premature mortality. More recent research has demonstrated that predicted biological age is sensitive to specific interventions. Human trials have reported that caloric restriction, a plant-based diet, lifestyle changes involving exercise, a drug regime including metformin, and vitamin D3 supplementation are all capable of slowing down or reversing an aging clock. Non-interventional studies have connected high-quality sleep, physical activity, a healthy diet, and other factors to age deceleration. Specific molecules have been associated with the reduction or reversal of predicted biological age, such as the antihypertensive drug doxazosin or the metabolite alpha-ketoglutarate. Although rigorous clinical trials are needed to validate these initial findings, existing data suggest that aging clocks are malleable in humans" - See metformin at ReliableRX, vitamin D at Amazon.com and alpha ketoglutarate at Amazon.com.
• Alpha-ketoglutarate attenuates colitis in mice by increasing Lactobacillus abundance and regulating stem cell proliferation via Wnt-Hippo signaling - Mol Nutr Food Res 2022 Feb 26 - "Collectively, the data provided herein demonstrated that α-KG administration attenuated mucosal inflammation, barrier dysfunction, and gut microflora dysbiosis. This beneficial effect was associated with increased Lactobacillus levels and regulated colon hyperplasia by the Wnt-Hippo signaling pathway"
• 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 Nov 30 - "The search continues for possible interventions that delay and/or reverse biological aging, resulting in extended healthspan and lifespan. Interventions delaying aging in animal models are well established; however, most lack validation in humans. The length of human lifespan makes it impractical to perform survival analysis. Instead, aging biomarkers, such as DNA methylation (DNAm) clocks, have been developed to monitor biological age. Herein we report a retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant®, an alpha-ketoglutarate based formulation, for an average period of 7 months. DNAm testing was performed at baseline and by the end of treatment with Rejuvant® supplementation. Remarkably, individuals showed an average decrease in biological aging of 8 years (p-value=6.538x10-12). Furthermore, the supplementation with Rejuvant® is robust to individual differences, as indicated by the fact that a large majority of participants decreased their biological age. Moreover, we found that Rejuvant® is of additional benefit to chronologically and biologically older individuals. While continued testing, particularly in a placebo-controlled design, is required, the nearly 8-year reversal in the biological age of individuals taking Rejuvant® for 4 to 10 months is noteworthy, making the natural product cocktail an intriguing candidate to affect human aging" - [Nutra USA] - See calcium alpha-ketoglutarate at Amazon.com.
• Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice - Cell Metab 2020 Sep 1 - "We find that CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines. We propose that induction of IL-10 by dietary AKG suppresses chronic inflammation, leading to health benefits. By simultaneously reducing frailty and enhancing longevity, AKG, at least in the murine model, results in a compression of morbidity" - See alpha ketoglutarate at Amazon.com.
• Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice - bioRxiv, 10/2019 - "Here we show that alpha-ketoglutarate (delivered in the form of a Calcium salt, CaAKG), a key metabolite in tricarboxylic (TCA) cycle that is reported to extend lifespan in worms, can significantly extend lifespan and healthspan in mice. AKG is involved in various fundamental processes including collagen synthesis and epigenetic changes. Due to its broad roles in multiple biological processes, AKG has been a subject of interest for researchers in various fields. AKG also influences several age-related processes, including stem cell proliferation and osteoporosis. To determine its role in mammalian aging, we administered CaAKG in 18 months old mice and determined its effect on the onset of frailty and survival, discovering that the metabolite promotes longer, healthier life associated with a decrease in levels of inflammatory factors. Interestingly the reduction in frailty was more dramatic than the increase in lifespan, leading us to propose that CaAKG compresses morbidity" - [Nutra USA] 
• Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: six-month study - Int J Vitam Nutr Res. 2007 Mar;77(2):89-97 - "This study suggests the potential usefulness of AKG-Ca in osteopenic postmenopausal women. AKG-Ca induced beneficial changes in serum CTX, which was consistent with preserving the bone mass in the lumbar spine"