Abstract
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 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. 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.