Sex differences in frailty: Comparisons between humans and preclinical models

Area of Science:

• Gerontology
• Physiology
• Sex Differences in Aging

Background:

• Frailty is a state of physiological decline, increasing vulnerability to stressors and adverse health outcomes.
• Clinical tools like the frailty index and frailty phenotype measure frailty.
• Studies indicate women are frailer than men, despite longer lifespans, presenting a paradox.

Purpose of the Study:

• To review evidence on male-female differences in frailty from clinical and animal studies.
• To highlight potential mechanisms contributing to sex differences in frailty.
• To explore the role of frailty in sex-specific susceptibility to age-related chronic diseases.

Main Methods:

• Literature review of clinical studies on frailty in humans.
• Review of preclinical animal models demonstrating sex differences in frailty.
• Examination of proposed biological and physiological mechanisms underlying these differences.

Main Results:

• Clinical data consistently show higher frailty levels in women compared to men.
• Preclinical animal models often replicate higher frailty in female animals.
• Evidence suggests sex-specific roles for frailty in chronic disease susceptibility.

Conclusions:

• Significant sex differences in frailty exist, with women generally exhibiting higher levels.
• Understanding the mechanisms behind these differences is crucial for targeted interventions.
• Further research in preclinical models is needed to elucidate the factors driving male-female frailty disparities in aging.