title: Telomeres and mitochondria in the aging heart.
abstract: 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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Javid
authors.initials: J
authors.lastname: Moslehi
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DePinho
authors.forename: Ergün
authors.initials: E
authors.lastname: Sahin
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D004734:Energy Metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism* / Q000648:ultrastructure; D059506:Telomere Shortening; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; C455622:PPARGC1B protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D019098:Telomerase