Researchers have found in an observational cohort study that a history of infections is significantly associated with higher frailty index scores in older adults, suggesting infections may contribute to the development of frailty. Frailty alone, as well as its combination with prior infections, was also linked to increased mortality risk, with obesity potentially influencing this relationship. The study was published in The Journals of Gerontology Series A by Francesco S. and colleagues.Frailty is a multidimensional clinical syndrome characterized by increased susceptibility to poor health outcomes, including disability, hospitalization, and death. Elderly individuals have been reported to have a high predisposition to infections due to the decline in the immune system; however, the long-term effects of infection history on the development of frailty and mortality have been poorly explored.The research was carried out using the data from the Baltimore Longitudinal Study of Aging (BLSA) involving 1,399 individuals. The population had a mean age of 65.3 years, with 51.5% being female. The infection history was based on the ICD-9 codes, which helped in the identification of individuals with a history of infections before the study.The research used the Frailty Index (FI), composed of 44 items, to measure the frailty status of the population. The relationship between the infection history and the individuals’ frailty was analyzed using multiple linear regression models, whereas the relationship between the infection history, frailty, and mortality was analyzed using Cox proportional hazard models. The research also analyzed the biological potential mediators, including plasma leptin levels and BMI, to see whether the metabolic factors played a role in the relationship between the infection history and the development of frailty.Key findings:The study had 1,399 participants from the Baltimore Longitudinal Study of Aging, with an average age of 65.3 years, of whom 51.5% were female.Previous history of infections had shown significant associations with the level of frailty. Previous infections, such as urinary tract infections, viral infections, pneumonia, and herpes virus infections, had strong associations with the level of frailty, as indicated by the Frailty Index. For the elderly population, 65 years and older, the previous history of infection had shown strong associations with the progression of frailty. As indicated, the hazard ratio for the history of infection was 1.43 (95% CI: 1.08–1.90, p = 0.02) for the transition from FI < 0.12 to FI ≥ 0.12. For the elderly population, the history of infection has shown strong associations with the progression of frailty. For the population with a history of infection and high levels of frailty, the risk of all-cause mortality was significantly high, with a hazard ratio of 1.12 (95% CI: 1.05–2.10, p = 0.02). Plasma leptin and BMI had shown positive mediator effects for the associations between the history of infection and the level of frailty.The study findings reveal that the history of infection may hasten the development of frailty and independently contribute to the risk of death in elderly individuals, especially in the presence of elevated levels of frailty and infection history. The mediator effect of leptin and BMI implies that the metabolic pathways of obesity may play a key role in the association between infection and frailty. The study findings emphasize the significance of preventing infection, managing metabolism, and assessing frailty as potential interventions for improving health outcomes in elderly individuals.Reference:Francesco Saverio Ragusa, Toshiko Tanaka, Michael R Duggan, Keenan A Walker, Nicola Veronese, Ligia J Dominguez, Mario Barbagallo, Luigi Ferrucci, Can Infections Drive Frailty? Insights from the Baltimore Longitudinal Study of Aging, The Journals of Gerontology: Series A, 2026 https://doi.org/10.1093/gerona/glag043