A new study has identified genetic variants linked to brain function, immune defence and metabolism that contribute to the development of frailty in older people. The study, published in Nature Aging by researchers from Karolinska Institutet, provides new biological insights into the onset of frailty.
Frailty – a condition in which the body loses its resilience and becomes more vulnerable to falls, infections and other stresses – increases the risk of hospitalisation and death. Understanding why some people are affected earlier than others can therefore be of great importance.
In a comprehensive genetic analysis of nearly one million people in Finland and the United Kingdom, researchers have found genetic variants linked to frailty. By analysing the participants' DNA and health data, the researchers were able to identify hundreds of genetic markers that influence the risk of developing the condition.
"Our results show that frailty is not caused by a single factor, but by many genes that affect how our immune system, brain and metabolism work. Some of these genes are completely new discoveries," says last author Juulia Jylhävä, associate professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
The results show that a person's genetic risk of frailty can be measured – and ultimately used to predict who is at increased risk of becoming ill or needing care, according to the researchers.
"In the future, we may be able to identify people who are at risk as early as middle age, when there is still time to prevent frailty. This opens the door to new ways of improving health in older people," concludes Juulia Jylhävä.
The study was conducted in collaboration with Tampere University in Finland. See the study for funders and any conflicts of interest.
Publication: 'Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty", Jonathan K.L. Mak, Chenxi Qin, Moritz Krüger, Anna Kuukka, FinnGen, Sara Hägg, Jake Lin, Juulia Jylhävä, Nature Aging, online 5 August 2025, doi: 10.1038/s43587-025-00925-y
