Ageing is widely assumed to make animals progressively more vulnerable to infection, an idea usually pinned on the gradual decline of the immune system. A new study in BMC Biology argues that this picture is incomplete. The work also shows that susceptibility measured at old age predicts remaining lifespan in males but not in females.
The team set out to test a hypothesis that departs from the standard narrative. Rather than treating rising infection susceptibility as a simple consequence of deteriorating immune defence, they proposed that age-related increases reflect changes in both resistance mechanisms, the bona fide immune processes that limit pathogen growth, and tolerance mechanisms, the physiological and metabolic processes that determine how much damage an infection causes. Crucially, they expected the relative importance of these two routes to vary between individuals, populations and sexes.
To capture that variation, the researchers assessed age-related susceptibility to bacterial pathogens across the outbred fly population and the 22 isolines. Leveraging this genetic diversity allowed them to investigate the relationship between infection susceptibility and lifespan, and to estimate how frequently increased susceptibility arises from declines in resistance versus declines in tolerance. The breadth of the survey mattered: susceptibility increased early in life and proved widespread across different infections and populations, indicating that this is not a quirk of one pathogen or one genetic background.
The sex comparisons produced a striking asymmetry. Baseline susceptibility and its change over age correlated strongly between males and females, yet susceptibility at old age did not correlate between the sexes.
Dissecting the mechanisms behind increased susceptibility revealed a clear pattern. Impaired resistance, the classical face of immunosenescence, did contribute to greater vulnerability. But the more frequent route was reduced tolerance, and this deficit could be detected early in life and remained low thereafter.
Perhaps the most consequential finding concerns lifespan. Susceptibility measured at old age predicted remaining lifespan in males only. The authors conclude that increased infection susceptibility is an early-arising ageing phenotype that occurs in both sexes but drives male mortality.
The study also quantified the shape of the susceptibility curve. Infection susceptibility followed a power-law, or Weibull, pattern rather than the exponential, or Gompertz, pattern that is typical of mortality. In practical terms, each doubling of age approximately doubled susceptibility.
On the basis of these results, the authors argue that the term immunosenescence should be reserved for dysregulation of resistance mechanisms alone. Extending it to cover all age-related increases in infection susceptibility, they contend, obscures the substantial contribution of tolerance, the ageing of non-immune physiological and metabolic functions, and the variation that exists between populations and between the sexes. A full understanding of why older animals lose control of pathogens, they write, requires consideration of population variation, sex and the ageing of non-immune functions.
Subject of Research: Age-related changes in infection susceptibility, disease tolerance and resistance in Drosophila melanogaster and their sex-dependent link to lifespan
Article Title: Harnessing variation in Drosophila melanogaster reveals different routes to increased infection susceptibility over age and sex-dependent association with lifespan
Article References: Monteiro-Black, B., Corbally, M.-K., Aleksandrowicz, J., Taggart, A. M., Langella, F., Belmonte, R. L., Mika, P., Duneau, D. F., & Regan, J. C. (2026). Harnessing variation in Drosophila melanogaster reveals different routes to increased infection susceptibility over age and sex-dependent association with lifespan. BMC Biology. https://doi.org/10.1186/s12915-026-02757-7
Image Credits: AI Generated
DOI: 10.1186/s12915-026-02757-7
Keywords: Drosophila melanogaster, infection susceptibility, ageing, disease tolerance, immunosenescence, lifespan, sex differences, bacterial pathogens, Weibull, Gompertz, resistance mechanisms, population variation
News Source: Beatrice Stafford. (November 4, 2026). Infection Susceptibility Rises Early in Ageing Flies and Predicts Lifespan Only in Males. Scienmag.
