AMPK as a Pro-longevity Target.
Chronic, age-associated diseases are already among the leading causes of morbidity and death in the world, a problem exacerbated by the rapidly rising proportion of elderly in the global population. This emergent epidemic represents the next great challenge for biomedical science and public health. Fortunately, decades of studies into the biology of aging have provided a head start by revealing an evolutionarily conserved network of genes that controls the rate and quality of the aging process itself and which can thereby be targeted for protection against age-onset disease. A number of dietary, genetic, and pharmacological interventions, including dietary restriction (DR) and the biguanide metformin, can extend healthy lifespan and reduce the incidence of multiple chronic conditions. Many of these interventions recurrently involve a core network of nutrient sensors: AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), the insulin/insulin-like growth factor signaling pathway (IIS), and the sirtuins. Here, we will summarize how AMPK acts downstream of these pro-longevity interventions and within this network of nutrient sensors to control the cell and physiological processes important for defining how well we age.
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA. kburkewi@hsph.harvard.edu.
Kristopher
K
Burkewitz
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA.
Heather J M
HJ
Weir
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA. wmair@hsph.harvard.edu.
William B
WB
Mair
D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D031204:Caloric Restriction; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000187:drug effects / Q000235:genetics*; D008687:Metformin / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D013002:Somatomedins / Q000235:genetics* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
D007328:Insulin; D021122:Protein Subunits; D013002:Somatomedins; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D037761:Sirtuins
AMPK; Aging; FOXO; Longevity; Metabolism; Mitochondria; Sirtuins; TOR