Are Lifespan and Healthspan Strongly Coupled?

Lifespan is length of life, while healthspan is length of healthy life. Are they strongly coupled? Is it possible to arrive at treatments that greatly alter one without much altering the other? A related concept is something that many researchers believe (or at least claim in public) that they are aiming for: compression of morbidity, in which healthspan is extended without lifespan being extended. It is hard to say how much of that is driven by the desire to avoid talking about life extension in the context of research, however, versus an earnest belief in the plausibility of the outcome. On the other side of that coin, it does seems plausible that the present bad strategy of trying to compensate for outcomes or ameliorate proximate causes of age-related disease - rather than address their root causes, the cell and tissue damage that causes aging - could be acting to marginally extend lifespan without extending healthspan. These are approaches that, at best, make suffering a chronic age-related condition a somewhat slower, somewhat less damaging process. It is a very expensive path to small gains, however. Keeping a damaged machine running without repairing that damage is a challenging undertaking, and far from the best approach to the problem.

Interventions that extend longevity in model laboratory organisms have proliferated. Traditionally, such interventions have been assumed to retard aging itself based on their ability to increase mean and maximum lifespan. The emphasis on longevity metrics alone made some sense in that longevity seemingly provides an unambiguous endpoint that has been assumed to be necessarily correlated with a general age-related physiological decline. While this may often be the case, it is not necessarily so. Indeed, human females live longer lives than males, but also suffer greater age-related morbidity by a number of measures. In laboratory species, long-lived worm genotypes are often outcompeted by shorter-lived genotypes and some evidence suggests that by a number of measures some long-lived worm genotypes are less healthy than the standard genotype even relatively early in life. As a major goal of basic aging research is to develop interventions that will enhance and prolong health in humans, it would be beneficial to the field to determine for all model organisms, which interventions extend health and which extend only life.

Because efforts to develop a cognate battery of tests to assess healthspan in mice and other model organisms have met with varying degrees of success we have taken a different approach. We feel that important indicators of health that can be commonly addressed in humans and in mice can be roughly categorized as those associated with age-related decreasing strength and mobility and those associated with decreasing cognitive capabilities. To this end, we present here an analysis of age-related change in commonly measured, noninvasive parameters associated with age-related changes in energetics, strength and mobility in the commonly used C57BL/6 mouse strain, and we determined to what extent these health parameters were associated with premature death. We measured age-related changes in healthspan in male and female 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.


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