Functional Aging in Male C57BL/6J Mice Across the Life-Span: A Systematic Behavioral Analysis of Motor, Emotional, and Memory Function to Define an Aging Phenotype

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.

SARS-CoV-2 infection results in lasting and systemic perturbations post recovery

“…To determine whether prolonged olfactory bulb inflammation was correlated with altered metrics on assays that assess affective behaviors, mock-, IAV-, and SARS-CoV-2-treated hamsters were subjected to a marble burying assay (Figure 6G-I). When hamsters were subjected to the this assay, an established metric for assessing rodent repetitive and anxiety-like behaviors (Yanai and Endo, 2021), SARS-CoV-2-infected animals demonstrated a significant reduction in burying activity compared to both mock and IAV groups, which performed comparably and were thus grouped together (Figure 6G). While several studies consider increased burying as a sign of elevated compulsiveness or anxiety-like behaviors, other studies have found that anxiogenic or compulsive behavior-inducing pharmacological substances can actually cause decreases in marble burying behavior that are well-below baseline (Jimenez-Gomez et al, 2011).…”

“…The marble burying assay was adapted from previously described protocols (Yanai and Endo, 2021). Hamsters were placed into a corner of a cage with clean bedding that had 20 equally-spaced glass marbles placed inside of it.…”

Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain

“…Likewise, cognitive decline is common between mice and humans [65], including reduction in spatial navigation performance (such as the Morris water maze in mice, or the equivalent in humans) [66]. Despite this, mouse cognitive decline seems to appear relatively sooner and faster than for humans [67], and decline in elaborate cognitive abilities specific to human, such as language, cannot be tested in animal models. Further, the neurogenic niche inhibited by T cells in aged mice [26] may not exist in humans [68].…”

Abnormal lipid droplets accumulation induced cognitive deficits in obstructive sleep apnea syndrome mice via JNK/SREBP/ACC pathway but not through PDP1/PDC pathway

“…The results of escape latency in the MWM test were examined through three-way mixed ANOVA (Champagne et al 2002 ). For the total traveling distance, platform crossing counts, the duration and distance in the target zone and the fear conditioning tests were assessed with two-way ANOVA (Yanai and Endo 2021 ). Other data were assessed with two-way ANOVA.…”