Apoptosis and aging: increased resistance to apoptosis enhances the aging process.
Apoptosis is a vital component in the evolutionarily conserved host defense system. Apoptosis is the guardian of tissue integrity by removing unfit and injured cells without evoking inflammation. However, apoptosis seems to be a double-edged sword since during low-level chronic stress, such as in aging, increased resistance to apoptosis can lead to the survival of functionally deficient, post-mitotic cells with damaged housekeeping functions. Senescent cells are remarkably resistant to apoptosis, and several studies indicate that host defense mechanisms can enhance anti-apoptotic signaling, which subsequently induces a senescent, pro-inflammatory phenotype during the aging process. At the molecular level, age-related resistance to apoptosis involves (1) functional deficiency in p53 network, (2) increased activity in the NF-κB-IAP/JNK axis, and (3) changes in molecular chaperones, microRNAs, and epigenetic regulation. We will discuss the molecular basis of age-related resistance to apoptosis and emphasize that increased resistance could enhance the aging process.
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. antero.salminen@uef.fi
Antero
A
Salminen
Johanna
J
Ojala
Kai
K
Kaarniranta
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D044127:Epigenesis, Genetic; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018832:Molecular Chaperones; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D048670:MAP Kinase Kinase 4