The intersection of frailty and metabolism

Cell Metab. 2024 May 7;36(5):893-911. doi: 10.1016/j.cmet.2024.03.012. Epub 2024 Apr 12.


On average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how metabolic diseases may modify the degree of frailty in old age and suggest that frailty may predispose toward metabolic disease. Metabolic interventions that can mitigate the degree of frailty in people are reviewed. New treatment strategies developed in animal models that are poised for translation to humans are also considered. We suggest that maintaining a youthful metabolism into older age may be protective against frailty.

Keywords: frailty index; frailty phenotype; metabolic dysregulation; metabolic syndrome; mouse models; protein restriction.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging* / metabolism
  • Animals
  • Energy Metabolism
  • Frail Elderly
  • Frailty* / metabolism
  • Humans
  • Metabolic Diseases / metabolism