Abstract
Cardiovascular disease is the leading cause of death in the United States, accounting for nearly one third of all mortalities [9]. While lifestyle modifications, drug development, and surgical technologies have increased the average life expectancy of humans, the risk and rates of heart disease continue to grow as the population ages. The process of aging causes unique physiological, histological, and biochemical changes in cardiac tissue. For example, aging cardiac myocytes are incapable of proliferation and cannot be reprogrammed transcriptionally in response to changes in workload [7]. Age-associated conditions such as buildup of reactive oxygen species, mechanical dysfunction, or other forms of trauma, have been linked to the development of hypertrophy and other cardiac pathologies [6,14]. Therefore, development of drugs that target age-dependent signaling pathways may provide promising therapeutic strategies for the treatment of heart disease.
Highlights
A study by Vinciguerra et al published in the January 2010 issue of Aging furnishes new and important information about the cellular mechanisms leading to the pathogenesis of heart failure [22]
Moderate overexpression (2.5 to 7-fold) of SIRT1 in transgenic mouse hearts protects against oxidative stress, and results in increased expression of antioxidants [1]
Vinciguerra et al hypothesize that SIRT1 and circulating IGF-1 play opposite roles, the local mIGF-1 isoform displays a novel cross-talk signaling program with SIRT1, which results in cardiomyocite protection from hypertrophic and oxidative stress
Summary
A study by Vinciguerra et al published in the January 2010 issue of Aging furnishes new and important information about the cellular mechanisms leading to the pathogenesis of heart failure [22] They propose a cardio-protective link between locally acting insulinlike growth factor (mIGF-1) and the NAD+-dependent deacetylase SIRT1. Vinciguerra et al hypothesize that SIRT1 and circulating IGF-1 play opposite roles, the local mIGF-1 isoform displays a novel cross-talk signaling program with SIRT1, which results in cardiomyocite protection from hypertrophic and oxidative stress. They show that mIGF-1-mediated activation of SIRT1 induces expression of the protective signaling molecules UCP1, adiponectin, and MT2 [22]. They conclude that the divergent signaling mechanisms between the two IGF-1 isoforms may account for their opposing effects in heart tissue (Figure 1)
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