Apoptosis and aging: increased resistance to apoptosis enhances the aging process

作者：Salminen Antero^*; Ojala Johanna; Kaarniranta Kai

来源：Cellular and Molecular Life Sciences, 2011, 68(6): 1021-1031.

DOI：10.1007/s00018-010-0597-y

• Aging
• Inflammaging
• NF-kappa B
• p53
• Cellular senescence
• Review

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-kappa B-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.

• 出版日期2011-3