Frailty and cytokines in preclinical models: Comparisons with humans

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 progres-sion. Preclinical models such as ageing and/or genetically modified mice offer a unique opportunity to mech-anistically 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 de-gree 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-alpha 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.

Automated summary

Persistent low-grade inflammation in aging individuals is associated with frailty, with interleukin-6 being a key pro-inflammatory cytokine linked to frailty progression. The relationship between other cytokines/chemokines and frailty remains uncertain, highlighting the need for further research to identify common inflammatory biomarkers for frailty in both humans and mice.