Abstract
We investigated effects of age, sex and frailty on contractions, calcium transients and myofilament proteins to determine if maladaptive changes associated with aging were sex-specific and modified by frailty. Ventricular myocytes and myofilaments were isolated from middle-aged (~12 mos) and older (~24 mos) mice. Frailty was assessed with a non-invasive frailty index. Calcium transients declined and slowed with age in both sexes, but contractions were largely unaffected. Actomyosin Mg-ATPase activity increased with age in females but not males; this could maintain contractions with smaller calcium transients in females. Phosphorylation of myosin-binding protein C (MyBP-C), desmin, tropomyosin and myosin light chain-1 (MLC-1) increased with age in males, but only MyBP-C and troponin-T increased in females. Enhanced phosphorylation of MyBP-C and MLC-1 could preserve contractions in aging. Interestingly, the age-related decline in Hill coefficients (r = −0.816; p = 0.002) and increase in phosphorylation of desmin (r = 0.735; p = 0.010), tropomyosin (r = 0.779; p = 0.005) and MLC-1 (r = 0.817; p = 0.022) were graded by the level of frailty in males but not females. In these ways, cardiac remodeling at cellular and subcellular levels is graded by overall health in aging males. Such changes may contribute to heart diseases in frail older males, whereas females may be resistant to these effects of frailty.
Highlights
Age modifies the heart, such changes are average responses that may not be present, or present to the same extent, in all individuals of the same age[10]
Calcium transients declined with age, but contractions were largely unaffected in both field-stimulated ventricular myocytes and intact hearts from male and female mice
Initial experiments determined whether ventricular myocyte contractions and the underlying calcium transients were affected by age and whether this differed between the sexes
Summary
Age modifies the heart, such changes are average responses that may not be present, or present to the same extent, in all individuals of the same age[10]. On average ventricular contractility declines with age, even though some older men and women perform at the same or even at higher levels when compared to younger adults[11]. One common technique is to create a “frailty index”, by dividing the number of health deficits in an individual by the total number of deficits considered to produce a score between 0 and 1, where higher scores denote greater frailty[18]. We have adapted this approach to quantify the degree of frailty in aging rodents[13,19,20,21]. Frailty was evaluated in each animal with a frailty index tool that measures frailty as the accumulation of health deficits across many diverse systems, but not the cardiovascular system per se[22]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call