Lifestyle, environment and other major determinants of frailty in older adults: a population-based study from the UK Biobank.

Frailty is a geriatric multidimensional syndrome characterized by a loss of physiologic reserves and disproportionate vulnerability to external stressors and associated with increased risk of multiple negative health outcomes. Since frailty can be prevented, controlled, and even reverted in its early stages, identifying the main factors involved in its development is crucial to implement preventive and/or restorative interventions. The aim of this study was to assess the impact of a broad range of parameters, including host factors, lifestyle, diet, and environmental and occupational conditions, on the development of frailty in later life. A cross-sectional study was conducted on 221,896 individuals aged 60 and over classified as non-frail (119,332, 53.8%), pre-frail (93,180, 42.0%), and frail (9384, 4.2%) according to the frailty phenotype. Using principal component analysis and machine learning to streamline the data, significant associations were found between frailty risk and air quality, diet, smoking, working conditions, and heavy alcohol consumption. Early-life factors, including breastfed as a baby and maternal smoking around birth, also emerged as predictors of frailty, which was further characterized by clinical indicators like polypharmacy, levels of C-reactive protein and other biomarkers of inflammageing. This study provided robust and original evidence on the association between a large battery of potential risk factors, from early to later stages of life, and the occurrence of frailty in older age. These results will contribute to the development of effective prevention strategies and facilitate the early detection of individuals at high risk of developing frailty.