Refeeding-associated AMPK<sub>γ1</sub> complex activity is a hallmark of health and longevity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37957359.
- Also identified by DOI 10.1038/s43587-023-00521-y and PMC identifier 10724066.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 AMPK<sub>γ1</sub> 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 AMPK<sub>γ1</sub> prevents metabolic quiescence and preserves healthy aging in vertebrates, offering potential avenues for intervention.
Medical subject headings
- Frailty
- Longevity