How cardiomyocyte excitation, calcium release and contraction become altered with age.

AbstractCardiovascular disease is the main cause of death globally, accounting for over 17 million deaths each year. As the incidence of cardiovascular disease rises markedly with age, the overall risk of cardiovascular disease is expected to increase dramatically with the aging of the population such that by 2030 it could account for over 23 million deaths per year. It is therefore vitally important to understand how the heart remodels in response to normal aging for at least two reasons: i) to understand why the aged heart is increasingly susceptible to disease; and ii) since it may be possible to modify treatment of disease in older adults if the underlying substrate upon which the disease first develops is fully understood. It is well known that age modulates cardiac function at the level of the individual cardiomyocyte. Generally, in males, aging reduces cell shortening, which is associated with a decrease in the amplitude of the systolic Ca2+ transient. This may arise due to a decrease in peak L-type Ca2+ current. Sarcoplasmic reticulum (SR) Ca2+ load appears to be maintained during normal aging but evidence suggests that SR function is disrupted, such that the rate of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)-mediated Ca2+ removal is reduced and the properties of SR Ca2+ release in terms of Ca2+ sparks are altered. Interestingly, Ca2+ handling is modulated by age to a lesser degree in females. Here we review how cellular contraction is altered as a result of the aging process by considering expression levels and functional properties of key proteins involved in controlling intracellular Ca2+. We consider how changes in both electrical properties and intracellular Ca2+ handling may interact to modulate cardiomyocyte contraction. We also reflect on why cardiovascular risk may differ between the sexes by highlighting sex-specific variation in the age-associated remodeling process. This article is part of a Special Issue entitled CV Aging

Reliability of a Frailty Index Based on the Clinical Assessment of Health Deficits in Male C57BL/6J Mice.

We investigated the reliability of a newly developed clinical frailty index (FI) that measures frailty based on deficit accumulation in aging mice. FI scores were measured by two different raters independently in a large cohort (n = 233) of 343–430 day-old male C57BL/6J mice. Inter-rater reliability was evaluated with correlation coefficients, the kappa statistic, and intra-class correlation coefficients (ICC) in three separate groups of mice (n = 45, 50, and 138 mice/group) sequentially over 3 months. After each group was evaluated, descriptions of techniques used to identify health deficits were amended. Mice had comparable overall FI scores regardless of rater (0.213±0.002 vs 0.212±0.002; p = .802), although discordant measures declined as techniques were refined. Correlation coefficients (r (2) values) between raters improved throughout the study and mean kappa values increased (mean ± SEM; 0.621±0.018, 0.764±0.017, and 0.836±0.009 for groups 1, 2, and 3; p < .05). Values for intra-class correlation coefficient also improved from .51 (95% confidence interval = 0.11–.73) to .74 (0.54–0.85) and .77 (0.67–.83). FI scores increased over 3 months (p < .05), but did not differ between raters. These results show a high overall inter-rater reliability when the clinical FI tool is used to assess frailty in a large cohort of mice