Unraveling Frailty Complexity: The Role of Genes and the Environment

Frailty is a complex, dynamic condition that predominantly affects older adults. It is characterized by a decrease in strength, endurance, and physiological function, which increases vulnerability to stressors. The Frailty Index (FI) measures frailty, defining it as the accumulation of health deficits. Frailty prevalence increases with age and is associated with adverse outcomes such as falls, disabilities, and mortality. Despite the significant impact of frailty on older adults’ health and quality of life, our understanding of the factors contributing to its progression remains limited. Specifically, the roles of genetic and environmental influences in shaping individual frailty trajectories over time are not well understood. Thus, this study investigated the sources of individual differences in longitudinal frailty trajectories, with a particular focus on genes and the environment.

To explore this, data from two NEAR studies were used: the Swedish Adoption/Twin Study of Aging (SATSA) and the Origins of Variance in the Oldest-Old: Octogenarian Twins (OCTO-Twin). SATSA included 1,842 adults aged 29–96 years who were followed up 15 times. The OCTO-Twin included 654 adults aged 79 and older who were followed up 5 times. Frailty was measured using the Frailty Index (FI).

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Frailty in older age is mainly due to environmental factors
The study found a much faster increase in the Frailty Index (FI) after 75 years. Twins from the earlier-born cohort had a higher mean FI at baseline but a slower increase rate afterward. FI levels at age 75 were moderately heritable in men (42%) and women (55%). Genetic influences were relatively stable across ages for men but increased for women. However, the most significant increase in FI variability after age 75 was due to individual-specific environmental influences for both sexes. Overall, determinants of frailty in late life are mainly due to environmental influences. This finding underscores the importance of targeting environmental risk factors to alleviate frailty in older adults. The study provides valuable insights into the complex interplay of genes and the environment in frailty progression, paving the way for more targeted interventions in the future.


Jonathan Mak, first author of the study. Photo: Gunilla Sonnebring

Mak JLK, Kuja-Halkola R, Bai G, Hassing LB, Pedersen NL, Hägg S, Jylhävä J, Reynolds CA. Genetic and Environmental Influences on Longitudinal Frailty Trajectories From Adulthood into Old Age. The Journals of Gerontology: Series A. 2023; 78 (2): 333 -341. https://doi.org/10.1093/gerona/glac197.