Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice

Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan an...

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Vydáno v:Cell metabolism Ročník 32; číslo 3; s. 447
Hlavní autoři: Asadi Shahmirzadi, Azar, Edgar, Daniel, Liao, Chen-Yu, Hsu, Yueh-Mei, Lucanic, Mark, Asadi Shahmirzadi, Arash, Wiley, Christopher D, Gan, Garbo, Kim, Dong Eun, Kasler, Herbert G, Kuehnemann, Chisaka, Kaplowitz, Brian, Bhaumik, Dipa, Riley, Rebeccah R, Kennedy, Brian K, Lithgow, Gordon J
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.09.2020
Témata:
frailty
inflammation
alpha-ketoglutarate
lifespan
longevity
healthspan
SASP
IL-10
ISSN:1932-7420, 1932-7420
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Abstract Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. 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.
AbstractList Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. 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.Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. 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.
Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. 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.
Author Kasler, Herbert G
Bhaumik, Dipa
Kaplowitz, Brian
Hsu, Yueh-Mei
Kim, Dong Eun
Lucanic, Mark
Gan, Garbo
Kuehnemann, Chisaka
Lithgow, Gordon J
Asadi Shahmirzadi, Arash
Riley, Rebeccah R
Asadi Shahmirzadi, Azar
Kennedy, Brian K
Wiley, Christopher D
Edgar, Daniel
Liao, Chen-Yu
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  surname: Asadi Shahmirzadi
  fullname: Asadi Shahmirzadi, Azar
  organization: The Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA; USC Leonard Davis School of Gerontology, University of Southern California, 3715 McClintock Ave., Los Angeles, CA 90191, USA
– sequence: 2
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  givenname: Garbo
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  organization: The Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA
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  email: bkennedy@nus.edu.sg
  organization: The Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA; Healthy Longevity Programme, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr., Singapore 117597, Singapore; Centre for Healthy Longevity, National University Health System, Singapore, 1E Kent Ridge Rd., Singapore 119228, Singapore; Singapore Institute of Clinical Sciences, A(∗)STAR, Singapore 117609, Singapore. Electronic address: bkennedy@nus.edu.sg
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  organization: The Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA; USC Leonard Davis School of Gerontology, University of Southern California, 3715 McClintock Ave., Los Angeles, CA 90191, USA. Electronic address: glithgow@buckinstitute.org
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ContentType Journal Article
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Keywords frailty
inflammation
alpha-ketoglutarate
lifespan
longevity
healthspan
SASP
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Snippet Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting,...
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