Human health does not unfold in isolation. Across the lifespan, social experiences including connection, safety, rejection, meaning, and belonging shape how individuals respond to the world. While these influences are often discussed in psychological or behavioral terms, research in human social genomics suggests they also extend into biology, influencing how genes are regulated over time.

Rather than altering DNA itself, social conditions and subjective perceptions appear to influence gene expression, determining which genes are more or less active at a given moment. Experiences such as loneliness, chronic social stress, or perceived threat can send biological signals that affect immune function, inflammation, and cognitive processes. In this framework, biology is not fixed or sealed off from lived experience. Instead, social context helps shape which genetic pathways are engaged across the lifespan.

Research Evidence Supporting Social Genomics

A growing body of human research supports this model. Studies examining immune gene expression consistently show that social adversity is associated with coordinated shifts in gene activity, including increased expression of proinflammatory genes and reduced expression of antiviral defense genes. This pattern, known as the Conserved Transcriptional Response to Adversity or CTRA, reflects how perceived threat can recalibrate immune signaling at the level of gene regulation.

Importantly, this response is more strongly associated with subjective experience than with objective circumstances. Feelings of loneliness, insecurity, or social threat predict gene expression patterns more reliably than measures such as marital status or social network size, underscoring the biological relevance of perception and belief.

Other studies demonstrate that beliefs can interact with genetic predispositions rather than simply acting alongside them. In a large longitudinal study of older adults, individuals with positive age beliefs showed significantly better cognitive outcomes over time. These beliefs amplified the cognitive benefit of a protective genetic variant, while negative beliefs suppressed it. Notably, positive age beliefs contributed far more to cognitive performance than the gene itself, offering direct evidence that self perceptions can shape how genetic potential is expressed.

Intervention studies add further nuance. Randomized trials of mindfulness based programs in older adults have shown reductions in activity of proinflammatory gene pathways, including NF kappa B signaling. However, these transcriptional changes were not accompanied by immediate reductions in circulating inflammatory proteins. This distinction highlights an important point. Shifts in gene regulation may represent upstream biological adaptations that do not always translate directly into short term changes in standard biomarkers.

Biological Mechanisms Linking Social Experience to Gene Expression

How do social experiences and beliefs translate into molecular change?

The process begins with neurocognitive appraisal. Social situations are interpreted by the brain as safe or threatening, supportive or hostile. When experiences are perceived as threatening, such as rejection, isolation, or chronic interpersonal stress, the central nervous system activates stress response pathways, including the sympathetic nervous system and the hypothalamic pituitary adrenal axis.

These systems release hormones and neurotransmitters that communicate with cells throughout the body. Rather than altering DNA, these signals influence transcription factors, proteins that regulate whether genes are transcribed into RNA. Transcription factors act like molecular dimmer switches, adjusting gene activity in response to internal and external cues.

One well characterized example is NF kappa B, a transcription factor that promotes proinflammatory gene expression. Stress related signaling can increase NF kappa B activity, shifting immune gene expression toward inflammation. When perceived threat is persistent, this signaling pattern may remain chronically engaged, even in the absence of physical danger.

Crucially, these pathways respond to perception, not just circumstance. Imagined or symbolic threats can activate the same biological responses as real ones, allowing beliefs and interpretations to shape gene regulation over time.

Clinical Implications

This research reinforces that social experience and perception are biologically relevant and can influence gene regulation pathways involved in inflammation, immune signaling, and resilience.

Clinically, this highlights the importance of identifying patterns that keep patients in a chronic stress response, such as persistent loneliness, negative beliefs about aging or illness, ongoing interpersonal conflict, or a sustained sense of threat or pressure. These factors can influence upstream biological signaling even when routine laboratory markers appear stable.

There is also evidence for specific, structured interventions that act on these pathways. Mindfulness Based Stress Reduction has been shown to reduce activity in proinflammatory gene networks such as NF kappa B. Cognitive Behavioral Therapy has demonstrated gene specific epigenetic effects, including changes in DNA methylation related to stress regulation and neural plasticity.

Taken together, these findings support integrating psychosocial assessment and targeted therapies to influence stress responsive pathways that shape health.

-Carey Kunz, ND, IFMCP

Director of Education at FMP Essentials

References

1. Slavich GM, Cole SW. The emerging field of human social genomics. Clin Psychol Sci. 2013;1(3):331-348. doi:10.1177/2167702613478594

2. Levy BR, Slade MD, Pietrzak RH, Ferrucci L. When culture influences genes: Positive age beliefs amplify the cognitive-aging benefit of APOE ε2. J Gerontol B Psychol Sci Soc Sci. 2021;76(4):660-668. doi:10.1093/geronb/gbaa126

3. Lindsay EK, Marsland AL, Cole SW, et al. Mindfulness-Based Stress Reduction reduces proinflammatory gene regulation but not systemic inflammation among older adults: A randomized controlled trial. Psychosom Med. 2024;86(2):130-140. doi:10.1097/PSY.0000000000001264

4. Buric I, Farias M, Jong J, Mee C, Brazil IA. What is the molecular signature of mind-body interventions? A systematic review of gene expression changes induced by meditation and related practices. Front Immunol. 2017;8:670. doi:10.3389/fimmu.2017.00670

5. Kusuma RM, Amelia VL, Phiri D, Chung MH. Nonpharmacologic interventions for altered DNA methylation in common mental disorders: A systematic review and meta-analysis. J Affect Disord. 2025;357:120953. doi:10.1016/j.jad.2025.120953