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Aging01:26

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Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
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Inflammaging and the sex-frailty paradox.

Beatrice Arosio1,2, Greta Salafia3, Evelyn Ferri3

  • 1Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, Via della Commenda 19, Milan, 20122, Italy. beatrice.arosio@unimi.it.

Aging Clinical and Experimental Research
|October 7, 2025
PubMed
Summary

Women exhibit the "sex-frailty paradox," being frailer but living longer than men. This study explored biological factors influencing frailty and longevity differences between sexes, revealing sex-specific biological roots.

Keywords:
AgingCytokinesFrailtyGender-differencesInflammation

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Area of Science:

  • Gerontology
  • Sex Differences in Aging
  • Biomarkers of Aging

Background:

  • The sex-frailty paradox describes women's higher frailty but lower mortality compared to men.
  • Biological, behavioral, and social factors may explain this paradox.
  • Understanding sex-specific biological mechanisms is crucial for aging research.

Purpose of the Study:

  • To investigate the distinct biological mechanisms of frailty and longevity in men and women.
  • To elucidate the underlying factors contributing to the sex-frailty paradox.

Main Methods:

  • Study included 452 participants (315 women, 137 men) stratified by age groups (≤80, 81-99, ≥100 years).
  • A 47-item frailty index was computed for all participants.
  • Plasma concentrations of inflammatory markers were analyzed using next-generation ELISA.

Main Results:

  • Younger women (≤80 years) were less frail; centenarian women (≥100 years) were more frail than men.
  • Similar frailty levels were observed between sexes in the 81-99 year age group.
  • Biomarkers increased with age but showed sex-specific associations with frailty, indicating distinct biological influences.

Conclusions:

  • Identifying unique molecular profiles in older men and women is essential for understanding the sex-frailty paradox.
  • Further research into sex-specific determinants of aging is needed.
  • This knowledge can inform strategies to enhance health and longevity in both sexes.