EXECUTIVE SUMMARY: PSYCHOSOCIAL FACTORS

Social isolation, loneliness, depression, and lack of purpose are not merely subjective states—they are biological conditions accelerating aging through measurable molecular mechanisms Loneliness activates CTRA (conserved transcriptional response to adversity), upregulating inflammatory genes and downregulating antiviral responses Social isolation increases mortality 25-50%, comparable to smoking or obesity Depression shortens telomeres, elevates inflammation, doubles dementia risk Purpose in life extends lifespan 15-20%, reduces cardiovascular events, preserves cognitive function.

Molecular mechanisms: HPA axis dysregulation creates glucocorticoid resistance and chronic inflammation Sympathetic nervous system activation triggers pro-inflammatory NF-κB signaling Chronic psychological stress accelerates epigenetic aging (1.65 years per loneliness unit) Depression and isolation impair immune function—reduced vaccine responses, latent virus reactivation, accelerated immunosenescence.

The mind-body connection is bidirectional: Psychosocial stress drives inflammation; inflammation induces depression-like symptoms (sickness behavior) This creates vicious cycles—loneliness causes inflammation, inflammation worsens mood and social withdrawal.

Evidence-based interventions (Grade A): Social connection programs (group activities, volunteering) reduce mortality 20-30% [17] Mindfulness-based stress reduction (MBSR) reverses CTRA, reduces inflammation, increases telomerase Cognitive behavioral therapy (CBT) treats depression and reduces inflammatory markers Purpose-in-life interventions extend healthspan Exercise provides dual benefits—direct anti-aging effects plus profound mood improvement.

Clinical approach: Screen elderly for social isolation, loneliness, and depression High-risk groups: Recent widowhood, living alone, severe illness, lack of family contact Interventions match severity—encourage social engagement for all, structured programs for isolated individuals, mental health treatment for clinical depression The goal: Maintain strong social connections, cultivate purpose and meaning, address depression promptly Psychosocial wellbeing is not optional for healthy aging—it's biological necessity Social connection is medicine Purpose is longevity Mental health is healthspan.