Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 292, Issue 3, Pages H1398-H1403Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01036.2006
Keywords
cardiomyocytes; contractile function; calcium regulatory protein; senescence
Funding
- NIAAA NIH HHS [1 R15-AA-13575-01] Funding Source: Medline
- NIA NIH HHS [1 R03-AG-21324-01] Funding Source: Medline
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Aging is associated with hepatic growth hormone resistance resulting in a fall in serum insulin-like growth factor 1 (IGF-1) level. However, whether loss of IGF-1 contributes to cardiac aging is unclear. This study was designed to examine the effect of cardiac overexpression of IGF-1 on cardiomyocyte contractile function in young (3 mo) and old (26-28 mo) mice. Cardiomyocyte contractile function was evaluated, including peak shortening (PS), time to 90% PS, time to 90% relengthening (TR90), and maximal velocity of shortening/relengthening (+/- dL/dt). Levels of advanced glycation end product, protein carbonyl, sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban, and Na+/Ca2+ exchanger were assessed by Western blot analysis. SERCA activity was measured by Ca-45(2+) uptake. Aging induced a decline in plasma IGF-1 levels. Aged cells exhibited depressed +/- dL/dt, prolonged TR90, and a steeper PS decline in response to increasing stimulus frequency compared with those in young myocytes. IGF-1 transgene alleviated aging-induced loss in plasma IGF-1 and aging-induced mechanical defects with little effect in young mice. The beneficial effect of IGF-1 transgene on aging-associated cardiomyocyte contractile dysfunction was somewhat mimicked by short-term in vitro treatment of recombinant IGF-1 (500 nM). Advanced glycation end product and protein carbonyl levels were higher in aged mice, which were not affected by IGF-1. Expression of SERCA2a (but not Na+/Ca2+ exchanger and phospholamban) and SERCA activity were reduced with aging, which was ablated by the IGF-1 transgene. Collectively, our data suggest a beneficial role of IGF-1 in aging-induced cardiac contractile dysfunction, possibly related to improved Ca2+ uptake.
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