Doctors talk about physical activity to reduce frailty but less attention is paid to biology. A new paper suggests that the hypothalamic–pituitary–gonadal (HPG) axis, the body’s system of regulating production of the hormone testosterone, can impact frailty.
"Suggests" means this is only EXPLORATORY, not human science, but a relationship between
HPG axis integrity and late-life frailty, based on observational work with dogs (thus the exploratory, dogs are not little people any more than mice are) found that lower mortality due to increasing frailty was erased in males with the longest gonad exposure. Activists will rush to invoke endocrine disruption the way they used to invoke epigenetics when it comes to chemicals, but that would be just speculation. Sex hormones were not measured.
What is not speculation is that old dogs can teach us new tricks. And have in this case.
Bort, the oldest living Rottweiler in North America at the time of the study. Credit: The Center for Exceptional Longevity Studies is part of the Gerald P. Murphy Cancer Foundation
The Exceptional Aging in Rottweilers Study is a cohort of dogs who have lived 30% longer than breed average — physiologically equivalent to 100-year-old humans — and uses questionnaires, medical records, and phone interviews with dog owners. For their hypothesis on gonad function fighting frailty, the authors created a frailty score using 34 clinical variables(1) in geriatric male dogs, estimated lifetime testis exposure and then followed them from frailty scoring until time of death. The 87 purebred male Rottweiler dogs resided in 85 households within 28 U.S states and Canada. Their median age at frailty scoring was 13.3 years. Median age at death was 14.0. Of the dogs, 27 had intact gonads at the time of scoring. In 57 dogs with reason for gonadectomy known (no intention to breed or done breeding), 17 had pre-existing health-related issues like hip /elbow dysplasia, etc. Owners said 13 of the 87 were considered overweight after seven years of age. The most common causes of death were cancer and neurological conditions.
The human relevance may come because there is a correlation between testosterone and muscle mass in older men but there is less confidence when testosterone, muscle strength, and physical function are considered. The impact of the HPG axis on preventing the adverse consequences of frailty once it occurs was shown in dogs. People who are less frail are psychologically more resilient and have greater life satisfaction.
For that reason, the biological underpinnings of the epidemiological relationship between HPG axis integrity and frailty resilience should be explored.
Citation: Waters, D.J., Maras, A.H., Fu, R. et al. Longer duration of intact hypothalamic–pituitary–gonadal (HPG) axis buffers the adverse impact of late-life frailty in male dogs. Sci Rep 15, 34467 (2025). https://doi.org/10.1038/s41598-025-20700-8
(1) Such as appetite, strength and stamina, sensory (eyesight, hearing), infection, urinary and fecal continence, sleep, mobility and balance, physical activity, mentation, cognition, pain, body condition, hair coat, current disease conditions (endocrine, cardiac, malignant neoplasia), and overall health
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