A cross-sectional study of male and female C57BL/6Nia mice suggests lifespan and healthspan are not necessarily correlated

Abstract

Lifespan provides a discrete metric that is intuitively appealing and the assumption has been that healthspan is extended concomitant with lifespan. Medicine has been more successful at extending life than preserving health during aging. Interventions that extend lifespan in model organisms do not always result in a corresponding increase in healthspan, suggesting that lifespan and healthspan may be uncoupled. To understand how interventions that extend life affect healthspan, we need measures that distinguish between young and old animals. Here we measured age-related changes in healthspan in male and female C57BL/6JNia mice assessed at 4 distinct ages (4 months, 20 months, 28 months and 32 months). Correlations between health parameters and age varied. Some parameters show consistent patterns with age across studies and in both sexes, others changed in one sex only and others showed no significant differences in mice of different ages. Few correlations existed among health assays, suggesting that physiological function in domains we assessed change independently in aging mice. With one exception, health parameters were not significantly associated with an increased probability of premature death. Our results show the need for more robust measures of murine health and suggest a potential disconnect between health and lifespan in mice.

Sex Differences in Age-related Impairments Vary across Cognitive and Physical Assessments in Rats

“…Univariate ANOVA for the latency to fall off of the rotamex machine that was used to test rotarod performance indicated that aged rats fell off in significantly less time than young rats (F[1,8] = 28.31; p < 0.001) and that male rats fell off in significantly less time than female rats (F[1,8] = 52.48; p < 0.001; Figure 2A). There was a trend for an interaction between age and sex that did not reach significance (F[1,8] = 4.24; p = 0.07), though a previous report has shown aged female mice aren't as susceptible to agerelated performance deficits at rotarod tasks as their male counterparts [37], which is consistent with the observations reported here. Univariate ANOVA for the speed at which rats fell off of the rotarod indicated aged rats fell off at significantly slower speeds than young rats (F[1,8] = 35.01; p < 0.001) and that males fell off at significantly slower speeds than females (F[1,8] = 65.34; p < 0.001; Figure 2B).…”

Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice

“…Six months later at 28–30 mo old a more limited set of Old Age testing was performed during weeks that the Cyclic KD group was eating control diet (Figure 2A). The goals of the healthspan studies were to identify any specific phenotypes that are strongly affected by Cyclic KD, and to test whether Cyclic KD broadly affects varied age-related phenotypes (Richardson et al, 2016) since lifespan and healthspan may not always be coupled in mice (Fischer et al, 2016). For the latter purpose, we combined diverse parameters into composite scores normalized as standard deviations below the mean young/baseline performance (Figure 2B).…”

Building strength, endurance, and mobility using an astaxanthin formulation with functional training in elderly

“…These mice were very old at the start of training given that 50% survivorship generally occurs about 28 months of age for this strain20 (vs. mean life expectancy of 78 years old for humans in the USA in 201321). The AX dose was determined for mice by scaling22 from the level found to be effective in rat studies 23.…”

“…Twenty-nine-month-old male mice were treated with either 300 mg/(kg × day) astaxanthin (n = 10, Astareal, Inc. Moses Lake, WA, USA) or standard chow alone (n = 9). These mice were very old at the start of training given that 50% survivorship generally occurs about 28 months of age for this strain 20 (vs. mean life expectancy of 78 years old for humans in the USA in 2013 21 ). The AX dose was determined for mice by scaling 22 from the level found to be effective in rat studies.…”