Abstract
Frailty is a geriatric syndrome that is an important public health problem for the older adults living in the USA. Although several methods have been developed to measure frailty in humans, we have very little understanding of its etiology. Because the molecular basis of frailty is poorly understood, mouse models would be of great value in determining which pathways contribute to the development of frailty. More importantly, mouse models would be critical in testing potential therapies to treat and possibly prevent frailty. In this article, we present data showing that Sod1KO mice, which lack the antioxidant enzyme, Cu/Zn superoxide dismutase, are an excellent model of frailty, and we compare the Sod1KO mice to the only other mouse model of frailty, mice with the deletion of the IL-10 gene. Sod1KO mice exhibit four characteristics that have been used to define human frailty: weight loss, weakness, low physical activity, and exhaustion. In addition, Sod1KO mice show increased inflammation and sarcopenia, which are strongly associated with human frailty. The Sod1KO mice also show alterations in pathways that have been proposed to play a role in the etiology of frailty: oxidative stress, mitochondrial dysfunction, and cell senescence. Using Sod1KO mice, we show that dietary restriction can delay/prevent characteristics of frailty in mice.
Highlights
Frailty is a clinical geriatric syndrome that is an important public health problem affecting a large proportion of older adults in the USA
We found that the Sod1KO mouse shows changes in pathways/processes that have been proposed to play a role in the etiology of frailty
Sod1KO mice exhibit a significant decrease in lifespan, suggesting that they might physiologically age more rapidly than WT mice and would be more prone to developing sarcopenia at a younger age
Summary
The cost of frailty, including costs from falls and disability, was estimated to be more than $18 billion in 2000 (Janssen et al 2004) This syndrome is recognized by geriatricians as a syndrome in which individuals show a progressive physical decline that is associated with increased medical comorbidity, disability, and mortality (Fried et al 2001; Woods et al 2005) even after taking common age-associated diseases and conditions into consideration (Fried and Walston 1998). Walston et al (2002) found in the Cardiovascular Health Study that frail individuals had increased mean levels of CRP compared to non-frail individuals (5.5 ± 9.8 vs 2.7 ± 4.0 mg/L) These peripheral blood markers persisted after exclusion of individuals with cardiovascular disease and diabetes, as well as after adjustment for age, sex, and race. Shrinking Weight loss (>10 lbs. lost unintentionally in prior year), sarcopenia (loss of muscle mass)
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