January 2025 Hot Topic: Loneliness, Epigenetics, and Accelerated Aging

By Machell Collier, MS
Senior Marketing and Clinical Content Specialist, IFM

Healthy aging is top of mind for many patients, and it is well known that modifiable lifestyle factors such as diet and exercise play a significant role in wellness and optimizing longevity. Continuing research also emphasizes the importance of maintaining social connections and supportive relationships to improve overall health and extend life expectancy.^1,2 In fact, loneliness has been identified as a pervasive public health concern worldwide, significantly associated with increased mortality risk.^3,4 Now, recent studies are adding more details about how loneliness impacts physiology at a genetic level and may contribute to accelerated aging.^5,6

Accelerated Aging & The Loneliness Factor

Global prevalence of loneliness has most recently been estimated at 26% overall, with approximately three out of ten adults over the age of 60 feeling lonely⁷ and an estimated prevalence of perceived loneliness among adolescents at 10.7% worldwide.⁸ Reflecting similar statistics, US-based 2024 polls report:

• One out of five adults experience daily feelings of loneliness.⁹
• An estimated 33% of older adults feel lonely some of the time or often.¹⁰
• 30% of young adults aged 18 to 34 feel lonely every day or several times a week.¹¹

In addition to increased risk of mortality, loneliness has also been associated with an increased risk of developing health conditions such as heart disease, stroke, type 2 diabetes,^12,13 and mild cognitive impairment.¹⁴ Researchers continue to clarify the physiological mechanisms involved with loneliness and its health impacts. To investigate how feeling lonely influences inflammatory, immunological, and age-related processes, two 2024 studies explored the connection between loneliness, DNA-methylation (DNAm), and epigenetic changes.^5,6 

In the 2024 Beam et al study, participants included 169 same-sex, adult-aged twins (aged 32-65 years) from the longitudinal Louisville Twin Study that started in 1957, measuring participants’ physical, cognitive, and psychosocial development.⁵ Investigators used whole blood samples and self-reported psychosocial questionnaires to assess loneliness levels and corresponding DNAm levels found at DNAm-specific sites across the human genome. They also tested the links between loneliness levels and six measures of DNAm age (i.e., epigenetic clocks).⁵ Investigators reported that:⁵

• Among the 837,274 sites analyzed, 25 suggestive sites were flagged because their DNAm levels increased with higher loneliness scores. Further analysis found that the 25 suggestive sites were associated with overexpressed genes in a mixture of biological processes and molecular functions, including inflammatory responses, metabolic processes, and oxygen delivery.
• Links between loneliness and DNAm age acceleration measures were small across all six epigenetic clocks. The statistically significant association was seen with the DunedinPACE clock, which specifically assesses how someone is aging across organ systems compared to their chronological age. Data from this clock suggested that among this population, higher levels of loneliness were significantly associated with higher average rates of physiological changes per year (i.e., accelerated epigenetic aging).

In the 2024 Freilich et al study, investigators explored associations between loneliness, epigenetic age acceleration, and multimorbidity later in life.⁶ Participants were from the Health and Retirement Study (n=4,018 US adults) who had provided blood draws, consented to DNAm assays, and completed loneliness and chronic disease assessments. Five different epigenetic clocks were used to assess methylation profiles and measure epigenetic age acceleration. The investigators reported the following:⁶

• A small, nominally positive association was seen between epigenetic age measurements and loneliness. However, loneliness did not fully reach statistical significance as a predictor of epigenetic age acceleration.
• Both loneliness scores and epigenetic age measurements predicted increasing chronic condition counts (i.e., multimorbidity). In addition, the measurement of DNAm levels using the GrimAge clock showed significant epigenetic mediation of loneliness-multimorbidity associations.

While both studies did not report overwhelming statistically significant findings, their results support and expand previous research, not only emphasizing the importance of social connection for healthy aging but highlighting additional avenues for further investigation into the mechanisms of loneliness and its influence on DNAm. As research continues to identify modifiable lifestyle factors including quality family and social relationships as protective factors for loneliness across the lifespan,^15,16 functional medicine clinicians continue to recognize the importance of these supportive relationships in a patient’s personalized therapeutic strategy and overall health journey.