Social relationships are crucial for mental health. On the other hand, social isolation and loneliness are associated with poorer health and early mortality risk. However, the biological mechanisms behind this remain obscure.
One approach to uncovering these mechanisms is by examining proteins in the blood. Proteins in the blood, produced by genes, are crucial for body function. They could be valuable drug targets, aiding researchers in developing new disease treatments.
A group of researchers from Fudan University in China and the University of Cambridge in the United Kingdom examined blood samples from more than 42,000 people aged between 40 and 69 in the UK Biobank.
They examined the proteomes- the suite of proteins – in blood samples to determine which proteins were more prevalent in socially isolated or lonely individuals and how these proteins were linked to worse health.
How do Close Relationships Lead to a Longer Life?
They found that interactions with friends and family may improve health by boosting the immune system and lowering the risk of diseases like heart disease, stroke, and type 2 diabetes.
The research team calculated social isolation and loneliness scores for individuals. Social isolation was measured objectively based on factors like living alone, frequency of social contact, and participation in social activities. At the same time, loneliness was subjective based on how individuals felt.
After analyzing the proteomes and considering factors such as age, sex, and socioeconomic status, the team identified 175 proteins linked to social isolation and 26 proteins associated with loneliness.
There was significant overlap, with about 85% of the proteins related to loneliness also linked to social isolation.
Many of these proteins are involved in inflammation, immune responses, and viral infections and have been connected to cardiovascular disease, type 2 diabetes, stroke, and early mortality.
The team explored the causal relationship between social isolation, loneliness, and protein levels using a statistical technique called Mendelian randomization. This approach allowed them to identify five proteins whose abundance was directly influenced by loneliness.
One protein found to be elevated due to loneliness was ADM, which is involved in stress response and the regulation of stress and social hormones, such as oxytocin—the “love hormone”—which helps reduce stress and improve mood. The team discovered a strong link between ADM levels and the size of the insula, a brain region responsible for interoception (the ability to sense internal bodily states).
Higher ADM levels were associated with a smaller insula volume and a smaller left caudate, a brain area related to emotions, reward, and social functions. Additionally, elevated ADM levels were connected to a higher risk of early death.
Another protein identified, ASGR1, is linked to higher cholesterol levels and an increased risk of cardiovascular disease. Other proteins found in the study are involved in developing insulin resistance, atherosclerosis (hardening of the arteries), and cancer progression, among other health issues.
Professor Jianfeng Feng from the University of Warwick stated, “There are over 100,000 proteins and many variants in the human body. AI and high-throughput proteomics can help us identify key proteins for the prevention, diagnosis, treatment, and prognosis of various diseases, potentially revolutionizing our understanding of human health.”
He added, “The proteins we’ve identified provide insights into the biology behind poor health in socially isolated or lonely individuals, underscoring the crucial role social relationships play in maintaining our health.”
Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “These findings drive home the importance of social contact in keeping us well. More and more people of all ages are reporting feeling lonely. That’s why the World Health Organization has described social isolation and loneliness as a ‘global public health concern’. We need to find ways to tackle this growing problem and keep people connected to help them stay healthy.”
Journal Reference:
- Shen, C et al. Plasma proteomic signatures of social isolation and loneliness associated with morbidity and mortality. Nat Hum Behav; 3 Jan 2025; DOI: 10.1038/s41562-024-02078-1