2023-11-13 マックス・プランク研究所
◆研究ではγ1サブユニットと呼ばれるタンパク質の活性低下が老化と関連しており、このサブユニットの活性を増加させると老魚は健康で長寿になりました。同様に、人間の高齢者サンプルでもγ1サブユニットの低いレベルが測定され、健康な老化に影響がある可能性が示唆されました。今後は、このサブユニットを活性化する分子を見つけ、老化に対する肯定的な影響を調査する予定です。
<関連情報>
- https://www.mpg.de/21105996/1113-balt-cycle-of-fasting-and-feeding-is-crucial-for-healthy-ageing-155436-x
- https://www.nature.com/articles/s43587-023-00521-y
摂食関連AMPKγ1複合体活性は健康と長寿の特徴である Refeeding-associated AMPKγ1 complex activity is a hallmark of health and longevity
Roberto Ripa,Eugen Ballhysa,Joachim D. Steiner,Raymond Laboy,Andrea Annibal,Nadine Hochhard,Christian Latza,Luca Dolfi,Chiara Calabrese,Anna M. Meyer,Maria Cristina Polidori,Roman-Ulrich Müller &Adam Antebi
Nature Aging Published:13 November 2023
DOI:https://doi.org/10.1038/s43587-023-00521-y
Abstract
Late-life-initiated dietary interventions show limited efficacy in extending longevity or mitigating frailty, yet the underlying causes remain unclear. Here we studied the age-related fasting response of the short-lived killifish Nothobranchius furzeri. Transcriptomic analysis uncovered the existence of a fasting-like transcriptional program in the adipose tissue of old fish that overrides the feeding response, setting the tissue in persistent metabolic quiescence. The fasting–refeeding cycle triggers an inverse oscillatory expression of genes encoding the AMP-activated protein kinase (AMPK) regulatory subunits Prkag1 (γ1) and Prkag2 (γ2) in young individuals. Aging blunts such regulation, resulting in reduced Prkag1 expression. Transgenic fish with sustained AMPKγ1 countered the fasting-like transcriptional program, exhibiting a more youthful feeding and fasting response in older age, improved metabolic health and longevity. Accordingly, Prkag1 expression declines with age in human tissues and is associated with multimorbidity and multidimensional frailty risk. Thus, selective activation of AMPKγ1 prevents metabolic quiescence and preserves healthy aging in vertebrates, offering potential avenues for intervention.
