Frailty and cytokines in preclinical models: Comparisons with humans

Mech Ageing Dev. 2022 Sep:206:111706. doi: 10.1016/j.mad.2022.111706. Epub 2022 Jul 12.

Abstract

Chronic low-grade elevations of blood-borne cytokines/chemokines in older age tend to associate with frailty in humans. This persistent inflammation is often called "inflammageing" and likely contributes to frailty progression. Preclinical models such as ageing and/or genetically modified mice offer a unique opportunity to mechanistically study how these inflammatory mediators affect frailty. In this review, we summarize and contrast evidence relating cytokines/chemokines to frailty in humans and in mouse models of frailty. In humans and mice, higher levels of the pro-inflammatory cytokine interleukin-6 regularly increased in proportion to the degree of frailty. Evidence linking other cytokines/chemokines to frailty in humans and mice is less certain. The chemokines CXCL-10 and monocyte chemoattractant protein-1 related to frailty across both species, but evidence is limited and inconsistent. Several other cytokines/chemokines, including tumour necrosis factor-α relate to frailty in humans or in mice, but evidence to date is species- and tissue-dependent. It is important for future studies to validate common mechanistic inflammatory biomarkers of frailty between humans and mice. Achieving this goal will accelerate the search for drugs to treat frailty.

Keywords: Ageing; Animal model; Inflammageing; Inflammation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokines
  • Cytokines*
  • Frailty*
  • Humans
  • Inflammation
  • Inflammation Mediators
  • Interleukin-6
  • Mice

Substances

  • Chemokines
  • Cytokines
  • Inflammation Mediators
  • Interleukin-6