Abstract
Aging is characterized generally by progressive and overall physiological decline of functions and is observed in all animals. A long line of evidence has established the laboratory mouse as the prime model of human aging. However, relatively little is known about the detailed behavioral and functional changes that occur across their lifespan, and how this maps onto the phenotype of human aging. To better understand age-related changes across the life-span, we characterized functional aging in male C57BL/6J mice of five different ages (3, 6, 12, 18, and 22 months of age) using a multi-domain behavioral test battery. Spatial memory and physical activities, including locomotor activity, gait velocity, and grip strength progressively declined with increasing age, although at different rates; anxiety-like behaviors increased with aging. Estimated age-related patterns showed that these functional alterations across ages are non-linear, and the patterns are unique for each behavioral trait. Physical function progressively declines, starting as early as 6 months of age in mice, while cognitive function begins to decline later, with considerable impairment present at 22 months of age. Importantly, functional aging of male C57BL/6J mouse starts at younger relative ages compared to when it starts in humans. Our study suggests that human-equivalent ages of mouse might be better determined on the basis of its functional capabilities.
Highlights
The population of aged individuals continues to grow in many developed countries (Prince et al, 2015; WHO, 2015), and the human lifespan has dramatically increased around the world (Dong et al, 2016)
Mice between the ages of 18 and 24 months are generally considered “old” (Flurkey et al, 2007), aging of mouse should be judged on the basis of its physiological functions
When we develop the interventions in mouse model of aging, we clearly know that it should be evaluated when their physiological function is sufficiently decreased but has a room for the improvement that provide the opportunity research on the intervention
Summary
The population of aged individuals continues to grow in many developed countries (Prince et al, 2015; WHO, 2015), and the human lifespan has dramatically increased around the world (Dong et al, 2016). As the term aging refers to the manifold changes that occur across an organism’s life-span (Kirkwood, 2005; da Costa et al, 2016), aging is thought of as occurring in an asynchronous and non-linear fashion in which several physical functions decline at the various rate (López-Otín et al, 2013; Rando and Wyss-Coray, 2021) The implications of these facts are that a holistic approach is needed in an aging research and that multiple physiological functions and behaviors of an aging organism need to be characterized at different stages of chronological age in order to properly describe an aging phenotype (Craig et al, 2015). The longer life-span of humans makes it difficult to study the biology of human aging over a reasonable time frame in research
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