Harnessing variation in Drosophila melanogaster reveals different routes to increased infection susceptibility over age and sex-dependent association with lifespan
Abstract
Background: It is widely accepted that susceptibility to infection increases with age, usually attributed to immune system dysregulation. However, factors beyond decreased resistance mechanisms may increase susceptibility, such as changes to physiological or metabolic processes determining overall tolerance, and this may differ between individuals. We hypothesised that age-related increases in susceptibility reflect changes in both immune system function and disease tolerance, with their relative importance varying by population and sex.
Results: We assessed age-related susceptibility to bacterial pathogens in an outbred Drosophila melanogaster population and 22 isolines. We leveraged this variation to investigate age-related infection susceptibility and lifespan and to estimate frequencies of declines in resistance or tolerance mechanisms. Susceptibility increased early in life and was widespread across infections and populations. Despite strong correlation between the sexes in baseline susceptibility and its decrease over age, susceptibility at old age did not correlate. Increased susceptibility was associated with impaired resistance ( bona fide immunosenescence), but more frequently with reduced tolerance, which could be detected early in life, and remained low. We find susceptibility at old age predicts lifespan in males only.
Conclusions: Increased infection susceptibility is an early-arising ageing phenotype occurring in both sexes and driving male mortality. Infection susceptibility followed a power-law (Weibull) rather than the exponential (Gompertz) pattern typical of mortality, with each doubling of age approximately doubling susceptibility. We argue that the term “immunosenescence” should be limited to dysregulation of resistance mechanisms, and consideration of population variation, sex, and ageing of non-immune functions is critical to fully understand age-related loss of pathogen control.
Related
- Wild ginseng adventitious roots restore sleep homeostasis in sleep-deprived Drosophila melanogaster
- A Wolbachia pipientis protein confers resistance to virus infection in Drosophila melanogaster
- Harnessing Enzymatic Diazotization for Chemoenzymatic N–N Bond Formation and Diversification
- Reliable and Efficient Agentic Protein Design with Toolset Harnessing
- Harnessing chia seed polysaccharides for green synthesis of copper-based nanoparticles with antidiabetic and anti-inflammatory activities
BibTeX
@article{monteiroblack2026harnessing,
title = {{Harnessing variation in Drosophila melanogaster reveals different routes to increased infection susceptibility over age and sex-dependent association with lifespan}},
author = {Barbara Monteiro-Black and Mary-Kate Corbally and Julia Aleksandrowicz and Adam M. Taggart and Francesco Langella and Rebecca L. Belmonte and Paulina Mika and David F. Duneau and Jennifer C. Regan},
journal = {BMC Biology},
year = {2026},
month = nov,
doi = {10.1186/s12915-026-02757-7},
url = {https://link.springer.com/article/10.1186/s12915-026-02757-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Harnessing variation in Drosophila melanogaster reveals different routes to increased infection susceptibility over age and sex-dependent association with lifespan
AU - Barbara Monteiro-Black
AU - Mary-Kate Corbally
AU - Julia Aleksandrowicz
AU - Adam M. Taggart
AU - Francesco Langella
AU - Rebecca L. Belmonte
AU - Paulina Mika
AU - David F. Duneau
AU - Jennifer C. Regan
PY - 2026
DA - 2026/11/03
JO - BMC Biology
DO - 10.1186/s12915-026-02757-7
UR - https://link.springer.com/article/10.1186/s12915-026-02757-7
AB - Background: It is widely accepted that susceptibility to infection increases with age, usually attributed to immune system dysregulation. However, factors beyond decreased resistance mechanisms may increase susceptibility, such as changes to physiological or metabolic processes determining overall tolerance, and this may differ between individuals. We hypothesised that age-related increases in susceptibility reflect changes in both immune system function and disease tolerance, with their relative importance varying by population and sex. Results: We assessed age-related susceptibility to bacterial pathogens in an outbred Drosophila melanogaster population and 22 isolines. We leveraged this variation to investigate age-related infection susceptibility and lifespan and to estimate frequencies of declines in resistance or tolerance mechanisms. Susceptibility increased early in life and was widespread across infections and populations. Despite strong correlation between the sexes in baseline susceptibility and its decrease over age, susceptibility at old age did not correlate. Increased susceptibility was associated with impaired resistance ( bona fide immunosenescence), but more frequently with reduced tolerance, which could be detected early in life, and remained low. We find susceptibility at old age predicts lifespan in males only. Conclusions: Increased infection susceptibility is an early-arising ageing phenotype occurring in both sexes and driving male mortality. Infection susceptibility followed a power-law (Weibull) rather than the exponential (Gompertz) pattern typical of mortality, with each doubling of age approximately doubling susceptibility. We argue that the term “immunosenescence” should be limited to dysregulation of resistance mechanisms, and consideration of population variation, sex, and ageing of non-immune functions is critical to fully understand age-related loss of pathogen control.
SN - 1741-7007
ER -