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Review
, 23 (Pt A), 90-100

Programmed Cell Death in Aging

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Review

Programmed Cell Death in Aging

John Tower. Ageing Res Rev.

Abstract

Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis. Mis-regulation of PCD is increasingly implicated in aging and aging-related disease. During aging the cell turnover rate declines for several highly-mitotic tissues. Aging-associated disruptions in systemic and inter-cell signaling combined with cell-autonomous damage and mitochondrial malfunction result in increased PCD in some cell types, and decreased PCD in other cell types. Increased PCD during aging is implicated in immune system decline, skeletal muscle wasting (sarcopenia), loss of cells in the heart, and neurodegenerative disease. In contrast, cancer cells and senescent cells are resistant to PCD, enabling them to increase in abundance during aging. PCD pathways limit life span in fungi, but whether PCD pathways normally limit adult metazoan life span is not yet clear. PCD is regulated by a balance of negative and positive factors, including the mitochondria, which are particularly subject to aging-associated malfunction.

Keywords: Aging; Apoptosis; Mitochondria; Necrosis; Sarcopenia; Senescence.

Figures

Figure 1
Figure 1
Cross-species comparison of PCD factors implicated in aging. The factors and regulatory relationships that appear similar between mammals, C. elegans and S. cerevisiae are emphasized; additional regulatory factors exist for each species but are not indicated for sake of clarity. For mammals the canonical intrinsic caspase-dependent apoptotic pathway is outlined. AIF and EndoG are caspase-independent and translocate to the nucleus where they mediate DNA fragmentation and chromatin condensation. Please see text for details.

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