Telomeres and mitochondria in the aging heart.

Moslehi J, DePinho RA, Sahin E
Circ Res. 2012 110 (9): 1226-37

PMID: 22539756 · PMCID: PMC3718635 · DOI:10.1161/CIRCRESAHA.111.246868

Studies in humans and in mice have highlighted the importance of short telomeres and impaired mitochondrial function in driving age-related functional decline in the heart. Although telomere and mitochondrial dysfunction have been viewed mainly in isolation, recent studies in telomerase-deficient mice have provided evidence for an intimate link between these two processes. Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and PGC-1β in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging.

MeSH Terms (16)

Age Factors Aging Animals Cardiovascular Diseases Carrier Proteins Energy Metabolism Heat-Shock Proteins Humans Mitochondria, Heart Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Signal Transduction Telomerase Telomere Telomere Shortening Transcription Factors Tumor Suppressor Protein p53

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