Human beings are inherently social. We thrive on connection, communication and shared experiences, which help shape our identities and foster a sense of belonging. Yet, in an increasingly digital and fast-paced world, feelings of loneliness and social isolation have become alarmingly common.

The World Health Organisation has stated that these feelings are widespread. About 25% of older people experience social isolation and 5-15% of adolescents feel lonely.

These figures are important since published studies have demonstrated that social isolation and loneliness are linked to increased risk of disease and death. Indeed, our own study, published in 2022, found that social isolation in older people carried a 26% increased risk of developing dementia. We also found that loneliness was associated with depression.

We wanted to follow up our previous study by understanding the underlying biological processes behind this link between social isolation and loneliness and health. Why is loneliness so bad for our bodies and minds?

Exploring proteins

We focused on proteomics, the study of proteins. This is because we know that proteins play a role in gene expression, the process by which the information encoded in a gene is turned into biological activity. Proteins are also a major source of drug targets for developing medications.

In this collaborative study between the University of Cambridge and Fudan University, published in Nature Human Behaviour, we used data from 42 062 participants from the UK Biobank and studied 2 920 plasma proteins.

We investigated the association between proteins and self-reported loneliness and social isolation. We discovered that the proteins found to be significantly associated with loneliness and social isolation are also known to be implicated in inflammation as well as antiviral and immune responses.

In particular, our study suggested that loneliness may lead to an increase in the levels of five specific proteins expressed in the brain (known as GFRA1, ADM, FABP4, TNFRSF10A and ASGR1). In other words, all the proteins we identified as related to loneliness were “positively associated”, meaning that people who feel lonely tend to have higher protein levels compared to those who do not feel lonely.

We also studied data that tracked the health of our participants for about 14 years. This found that more than half of the proteins were linked to cardiovascular disease, type 2 diabetes, stroke and death.

Based on our findings, having good social relationships and not feeling lonely may promote health by reducing the levels of certain harmful proteins. However, proteins may only partly explain the link between loneliness and health. Other potential pathways, such as social stress, may also play a role.

To our knowledge, this may be the first demonstration of how loneliness affects morbidity and mortality through its association with these five key proteins.

Societal impacts

Social isolation and loneliness affect all ages and genders and leads to major mental and physical health problems. This study helps to understand how this happens on a biological level.

It demonstrates how important it is to connect with others through social activities, for example volunteering or team sport. This can reduce the effects of social isolation and loneliness on the underlying biological processes important for health outcomes.

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While technology offers new ways to stay in touch, it can sometimes lead to superficial connections that leave us feeling more disconnected than ever. This paradox — being surrounded by digital interactions yet feeling profoundly alone — underscores the importance of deep, meaningful social connections.

Face-to-face social interactions where you also experience non-verbal communication often fosters better connections. Indeed, one study showed that partners communicating face to face had more positive impressions than people interacting via a computer.

Social interactions are ultimately essential for our well-being, boosting both physical and mental health. Social connections reduce stress, lower blood pressure and support immune function. They also enhance cognitive health and improve brain health. In addition, they can foster empathy and understanding, strengthening our minds and providing emotional resilience.

Clearly, to foster a flourishing society we need to build meaningful connections with one another.
The authors are Barbara Jacquelyn Sahakian, is professor of clinical neuropsychology, University of Cambridge; Christelle Langley, postdoctoral research associate, cognitive neuroscience, University of Cambridge; Chun Shen, postdoctoral research fellow of neuroscience, Fudan University; and Jianfeng Feng, professor of science and technology for brain-inspired intelligence/computer science, Fudan University