The relationship between parity and late-life frailty: companion dogs as a preclinical model for evaluating factors that aggravate or mitigate the frailty cost of reproduction

Frailty refers to a state of heightened vulnerability to adverse health outcomes. Animal models of frailty provide an opportunity to probe lifetime events and exposures that drive frailty progression and to evaluate intervention strategies that could mitigate frailty development and its consequences in older adults. The relationship between parity-production of live offspring-and later life frailty in women is poorly understood. Here, we utilize companion dogs to test the hypothesis that production of live offspring comes at a physiological cost, leading to increased late-life frailty. We measured deficit accumulation using a 34-item clinical frailty index in a cohort of 95 geriatric female Rottweilers. The study outcome was late-life robustness, defined as the lowest quintile of frailty in the study population. We found no evidence of reproductive cost. Instead, compared to nulliparous females, parous females were 3× more likely to retain late-life robustness [OR, 95% CI = 3.30,1.16-9.38; p = .025], a relationship not attenuated by adjusting for covariates, including owner-reported reason for nulliparity. Moreover, females with largest number of litters had highest late-life robustness. Finally, employing two measures of early-life health/fitness-earlier-in-life health deficits, lifetime morbidity profiles-could not explain results based on selection. This inquiry introduces a new application of the dog model of frailty for the study of reproduction and deficit accumulation. The linkage we observed between parity and higher late-life robustness is congruent with results of several studies in women, suggesting parous females may have the capacity to dampen the development of later-in-life frailty, which should be further investigated at the genetic and epigenetic level.