Academic Journal
Refeeding-associated AMPKγ1 complex activity is a hallmark of health and longevity
| العنوان: | Refeeding-associated AMPKγ1 complex activity is a hallmark of health and longevity |
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| المؤلفون: | Ripa, Roberto, Ballhysa, Eugen, Steiner, Joachim D., Laboy, Raymond, Annibal, Andrea, Hochhard, Nadine, Latza, Christian, Dolfi, Luca, Calabrese, Chiara, Meyer, Anna M., Polidori, Maria Cristina, Müller, Roman-Ullrich, Antebi, Adam |
| المساهمون: | Ripa, Roberto, Ballhysa, Eugen, Steiner, Joachim D., Laboy, Raymond, Annibal, Andrea, Hochhard, Nadine, Latza, Christian, Dolfi, Luca, Calabrese, Chiara, Meyer, Anna M., Polidori, Maria Cristina, Müller, Roman-Ullrich, Antebi, Adam |
| سنة النشر: | 2023 |
| المجموعة: | Scuola Normale Superiore: CINECA IRIS |
| مصطلحات موضوعية: | hydroxymethylglutaryl coenzyme A reductase kinase, transcriptome, transfer RNA, triacylglycerol, adipose tissue, adult, aged, aging, AMPK signaling, animal experiment, anorexia, antibody labeling, antigen retrieval, Article, bioenergy, body weight, chemoluminescence, CRISPR-CAS9 system, diencephalon, DNA extraction, female, food intake, frailty, Fulton index, gene editing, gene expression, gene mutation, gene overexpression, genetic transcription, glucose blood level |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37957359; volume:3; issue:12; firstpage:1544; lastpage:1560; numberofpages:17; journal:NATURE AGING; https://hdl.handle.net/11384/146364 |
| DOI: | 10.1038/s43587-023-00521-y |
| الاتاحة: | https://hdl.handle.net/11384/146364 https://doi.org/10.1038/s43587-023-00521-y |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.ED1967F6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s43587-023-00521-y |
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