Phenotypical, Behavioral, and Systemic Hallmarks in End-Point Mouse Scenarios

Abstract

Highlights: Husbandry homecage behavior and a physical frailty phenotype point to end-point status in mice. Piloerection is the best gross examination hallmark of 16-month-old mice at end-point. Structural kyphosis characterizes end-point mice, while postural kyphosis indicates normal aging. WAT loss and hepatic and splenomegaly indexes can be indirect measures of sarcopenia. Carcass index correlates with piloerection and kyphosis in end-point mice. The state of frailty is a clinical–biological syndrome that affects the older population with a higher risk of functional dependence. Animal models can provide a tool to study this complex scenario. In the present work, we analyzed the physical and behavioral hallmarks of end-point status in 16-month-old mice (C57BL/6J) according to animal welfare regulations compared to age-matched counterparts with normal aging. A group of 6-month-old mice was added to control for age bias. First, we identified ‘structural kyphosis’ (visible and unmodifiable deformation in locomotion) correlated with piloerection as the hallmarks of the physical frailty phenotype compared to the ‘postural kyphosis’ (adjustment to counteract increased visceral volume but attenuated during locomotion) of old mice with normal aging. Alopecia (barbering) was presented in both old groups. Normal levels of exploratory activity in the corner test for neophobia and triceps surae muscle weight but an increased latency of rearing indicated the poorest emotional phenotype, with a possible contribution of structural kyphosis. The presence of hepatomegaly and splenomegaly counteracted the significant WAT loss commonly associated with end-of-life traits, which should have a normal body weight but preserved muscle mass.