Deficiency of insulin-like growth factor 1 reduces sensitivity to aging-associated cardiomyocyte dysfunction.

Rejuvenation Research
Qun LiJun Ren

Abstract

Circulating insulin-like growth factor-1 (IGF-1) levels are linked to cardiac performance and lifespan. However, the role of IGF-1 levels in aging-associated cardiac dysfunction has not been defined. This study was designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on aging-induced cardiomyocyte contractile and intracellular Ca(++) dysfunction. Cardiomyocytes were isolated from young (2- to 4-month-old) and old (24- to 26-month-old) male C57BL/6 and LID mice. Cardiomyocyte contractile and intracellular Ca(++) transient properties were evaluated, including peak shortening (PS), maximal velocity of shortening/relengthening (+/-dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), electrically stimulated change in fura-fluorescence intensity (DeltaFFI), and intracellular Ca(++) decay rate. Aged C57BL/6 myocytes displayed reduced PS, +/-dL/dt and DeltaFFI as well as prolonged TR(90) and intracellular Ca(++) decay. IGF-1 deficiency decreased +/-dL/dt, and prolonged TR(90) with little change in other mechanical indices. Interestingly, LID dampened aging-induced changes in cardiomyocyte function. Aging and IGF-1 deficiency both contributed to whole-body glucose intolerance. Aging downregulated expression of...Continue Reading

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