Researchers from the UK (Universities of Cambridge and Warwick) and China drew this conclusion after studying proteins from blood samples taken from over 42,000 adults recruited to the UK Biobank. Their findings were published recently in the journal Nature Human Behaviour (Shen, 2025).
Evidence increasingly demonstrates that both social isolation and loneliness are linked to poorer health and an early death. Despite this evidence, however, the underlying mechanisms through which social relationships impact health remain elusive.
This team examined ‘proteomes’ (a suite of proteins) in blood samples donated by over 42,062 adults aged 40-69 years who are taking part in the UK Biobank. This allowed them to see which proteins were present in higher levels among people who were socially isolated or lonely, and how these proteins were connected to poorer health.
Social isolation is an objective measure based on, for example, whether someone lives alone, how frequently they have contact with others socially, and whether they take part in social activities. Loneliness, on the other hand, is a subjective measure based on whether an individual feels lonely.
When they analysed the proteomes and adjusted for factors such as age, sex and socioeconomic background, the team found 175 proteins associated with social isolation and 26 proteins associated with loneliness (though there was substantial overlap, with approximately 85% of the proteins associated with loneliness being shared with social isolation).
Many of these proteins are produced in response to inflammation, viral infection and as part of our immune responses, as well as having been linked to cardiovascular disease, type 2 diabetes, stroke, and early death.
The team then used a statistical technique known as Mendelian randomisation to explore the causal relationship between social isolation and loneliness on the one hand, and proteins on the other. Using this approach, they identified five proteins (GFRA1, ADM, FABP4, TNFRSF10A and ASGR1) whose abundance was caused by loneliness. Dr Chun Shen, the lead author, said:
We know that social isolation and loneliness are linked to poorer health, but we’ve never understood why.
Our work has highlighted a number of proteins that appear to play a key role in this relationship, with levels of some proteins in particular increasing as a direct consequence of loneliness.”
Why and how isolation and loneliness could affect protein production is unknown.
