Regulation of the aging process by autophagy.
Autophagy is involved in cellular protein and organelle degradation, which is mediated by the lysosomal pathway. Autophagocytosis has a key role in cellular housekeeping by removing damaged organelles. During aging, the efficiency of autophagic degradation declines and intracellular waste products accumulate. In Caenorhabditis elegans, there is clear evidence that lifespan is linked to the capacity to regulate autophagy. Recent studies have revealed that the same signaling factors regulate both aging and autophagocytosis, thus highlighting the role of autophagy in the regulation of aging and age-related degenerative diseases. Here, we examine in detail the interactions of the signaling network involving longevity factors SIRT1, mTOR, FoxO3, NF-kappaB and p53 in the regulation of autophagy. We discuss the possibility that these well-known stress resistance and longevity factors regulate the aging process via autophagy.
Salminen
Antero
A
Department of Neurology, Institute of Clinical Medicine, University of Kuopio, P.O. Box 1627, Kuopio FIN-70211, Finland. antero.salminen@uku.fi <antero.salminen@uku.fi>
Kaarniranta
Kai
K
D000375:Aging / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D017173:Caenorhabditis elegans; D004358:Drug Therapy / Q000639:trends; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D051550:I-kappa B Kinase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins