Growth hormone receptor knockout (GHRKO) mice are smaller, age more slowly, and live considerably longer than their unaltered peers. Researchers have yet to create a longer-lived mouse lineage. Interestingly, and perhaps unfortunately for the prospects of slowing aging in our species, similar human mutants do not appear to live longer than the rest of us. Much the same is true of the practice of calorie restriction: long-lived mice, tremendous health benefits in both mice and humans, but no signs of greatly extended life in humans.
Aging more slowly, either through disruption of growth hormone metabolism or through calorie restriction, means that all measures of degeneration are impacted - such as the frailty and muscular weakness examined by these researchers:
Neuromusculoskeletal (physical) frailty is an aging-attributable biomedical issue of extremely high import, from both public health and individual perspectives. Yet, it is rarely studied in nonhuman research subjects and very rarely studied in animals with extended longevity. In an effort to address this relatively neglected area, we have conducted a longitudinal investigation of the neuromusculoskeletal healthspan in mice with two senescence-slowing interventions: growth hormone (GH) resistance, produced by GH receptor "knockout" (GHR-KO), and caloric restriction (CR).
We report marked improvements in the retention of strength, balance, and motor coordination by the longevity-conferring GHR/BP gene disruption, CR regimen, or a combination of the two. Specifically, GHR-KO mice exhibit superior grip strength, balance, and motor coordination at middle age, and CR mice display superior grip strength at middle age. The advantageous effects established by middle-age are more pronounced in old-age, and these robust alterations are, generally, not gender-specific. Thus, we show that genetic and/or dietary interventions that engender longevity are also beneficial for the retention of neuromusculoskeletal health and functionality. The translational knowledge to be gained from subsequent molecular or histological investigations of these models of preserved functionality and decelerated senescence is potentially relevant to the efforts to reduce the specter of fear, falls, fracture, and frailty in the elderly.