Assessing Health in Aging Male and Female Mice: Does Cardiac Function Dictate Frailty or Physical Resilience?

As the global population over age 65 is projected to triple by 2050, understanding the physiological mechanisms of aging and the role of sex as a biological variable (SABV) is critical. Research conducted on old mice demonstrates that age-related cardiac dysfunction is differentially linked to markers of frailty and resilience in a sex-dependent manner. We assessed post-anesthesia recovery time, wire hanging test, and a deficit accumulation-based frailty index as markers of whole-body frailty and resilience, and correlated these variables with cardiac parameters obtained by echocardiography and Doppler imaging in 25-26-month-old mice. The results demonstrated significant heterogeneity across all functional parameters in both groups. Male and female aging profiles are distinct: in males, higher frailty scores are primarily associated with cardiac hypertrophy and increased body surface area (BSA). In contrast, female mice exhibit a more complex relationship in which hyperdynamic cardiac markers (such as increased aortic peak velocity) correlate with prolonged recovery from systemic stressors like anesthesia. Crucially, the three primary functional assessments used-the frailty index, anesthesia recovery time, and the wire hanging test-did not strongly correlate with each other, indicating that they measure interrelated yet distinct aspects of biological vulnerability and physiological reserve. These findings underscore the necessity of sex-disaggregated data and multi-metric assessments in geroscience to develop effective, personalized strategies for extending healthspan.