Psilocybin Effects on Healthy Aging Biomarkers and Purpose in Life

Aging is accompanied by progressive changes across multiple physiological systems that contribute to functional decline and increased risk for age-related disease. Biomarkers of biological aging, including DNA methylation-based epigenetic clocks, have emerged as tools for assessing age-related biological processes and predicting future health outcomes.

Recent preclinical studies have suggested that psilocybin and its active metabolite, psilocin, may influence several pathways implicated in aging, including cellular senescence, oxidative stress, neuroplasticity, and epigenetic regulation. In addition to biological effects, observational studies have demonstrated associations between psychosocial factors, including purpose in life and social connectedness, and reduced morbidity and mortality in older adults. Previous clinical studies have shown that psilocybin may produce changes in psychological well-being, meaning, and related constructs.

The LONG-LIFE Study is designed to evaluate multiple domains relevant to healthy aging, including, but not limited to, epigenetic and biological clock measures, cognitive performance, psychosocial well-being, and ecological momentary assessments of daily experience.

• Psilocybin (Usona Institute) (Drug): 25mg capsule of psilocybin

Primary outcomes

• Change in Epigenetic/Biological Clock Profiling from Baseline to Week 4 and Week 16 [Change from Baseline to Week 4 and Week 16]: Epigenetic/biological clock profiles; change from Baseline to Week 4 and 16
• Change in Purpose in Life (PIL) from Baseline to Week 4 and Week 16 [Change from Baseline to Week 4 and Week 16]: Change from baseline in Purpose in Life score measured using the 7-item Purpose in Life Scale (PIL) from the Health and Retirement Study (score range 1-6; higher scores indicate greater purpose in life).

Secondary outcomes

• Change in Epigenetic/Biological Clock Profiling from Baseline to Week 52 [Change from Baseline to Week 52]: Change in Epigenetic/biological clock profile from Baseline to Week 52
• Change in Telomere Length from Baseline to Week 52 [Change from Baseline to Week 52]
• Change in Purpose in Life (PIL) from Baseline to Week 52 [Change from Baseline to Week 52]: Change from baseline in Purpose in Life score measured using the 7-item Purpose in Life Scale (PIL) from the Health and Retirement Study (score range 1-6; higher scores indicate greater purpose in life).
• Change in Satisfaction with Life from Baseline to Week 4 and Week 16 [Change from Baseline to Week 4 and Week 16]: Measured using the Satisfaction With Life Scale (SWLS). Scores range from 5 to 35, where higher scores indicate greater satisfaction with life.
• Change in Wellbeing from Baseline to Week 4 and Week 16 [Change from Baseline to Week 4 and Week 16]: Measured using the Warwick Edinburgh Mental Well-Being Scale (WEMWBS). Scores range from 14 to 70, with higher scores indicating higher mental wellbeing.
• Change in Optimism from Baseline to Week 4 and Week 16 [Change from Baseline to Week 4 and Week 16]: Measured using the Life Orientation Test - Revised (LOT-R). Scores range from 0 to 24, with higher scores indicating higher dispositional optimism.
• Change in Perceived Control/Mastery from Baseline to Week 4 and Week 16 [Change from Baseline to Week 4 and Week 16]: Measured using the Pearlin Mastery Scale (PM). Scores range from 7 to 28; higher totals indicate greater self-mastery.
• Change in Loneliness from Baseline to Week 4 and Week 16 [Change from Baseline to Week 4 and Week 16]: Measured using the 3-Item UCLA Loneliness Scale (UCLA-3). Scores range from 3 to 9. Higher scores indicate a greater degree of loneliness.

Sex: All, ages: 60 Years to 80 Years, accepts healthy volunteers

Inclusion Criteria:

* English speaking and able to provide informed consent and complete study procedures
* Medically healthy, as determined by the screening physician, with no significant medical conditions that would interfere with participation or affect the safety of the subject.

Exclusion Criteria:

* History or presence of any psychiatric or medical condition that, in the opinion of the investigator, could pose a safety risk, interfere with participation, or confound study results.
* Abnormal ECG at screening that may increase risk during participation (e.g., prolonged QTc, arrhythmias, or other clinically significant findings as determined by the study physician).
* Unwilling or unable to discontinue medications that may interfere with study participation, as determined by the investigator.