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Mol Cell. 2010 Oct 22;40(2):333-44. doi: 10.1016/j.molcel.2010.10.002.

The aging stress response.

Author information

1
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. marcia_haigis@hms.harvard.edu

Abstract

Aging is the outcome of a balance between damage and repair. The rate of aging and the appearance of age-related pathology are modulated by stress response and repair pathways that gradually decline, including the proteostasis and DNA damage repair networks and mitochondrial respiratory metabolism. Highly conserved insulin/IGF-1, TOR, and sirtuin signaling pathways in turn control these critical cellular responses. The coordinated action of these signaling pathways maintains cellular and organismal homeostasis in the face of external perturbations, such as changes in nutrient availability, temperature, and oxygen level, as well as internal perturbations, such as protein misfolding and DNA damage. Studies in model organisms suggest that changes in signaling can augment these critical stress response systems, increasing life span and reducing age-related pathology. The systems biology of stress response signaling thus provides a new approach to the understanding and potential treatment of age-related diseases.

PMID:
20965426
PMCID:
PMC2987618
DOI:
10.1016/j.molcel.2010.10.002
[Indexed for MEDLINE]
Free PMC Article
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