A new mouse model of frailty: the Cu/Zn superoxide dismutase knockout mouse

Sathyaseelan S. Deepa, Shylesh Bhaskaran, Sara Espinoza, Susan V. Brooks, Anne McArdle, Malcolm J. Jackson, Holly Van Remmen, Arlan Richardson

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)187-198
Number of pages12
JournalGeroScience
Volume39
Issue number2
DOIs
StatePublished - Apr 1 2017

Keywords

  • Cu/Zn superoxide dismutase
  • Frailty
  • Inflammation
  • Oxidative stress
  • Sarcopenia
  • Senescence

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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