PRecision gerOMedicinE: Tailored Healthy agEing With Lifestyle, sUpplements and drugS (PROMETHEUS)

PRecision gerOMedicinE: Tailored Healthy agEing With Lifestyle, sUpplements and drugS (PROMETHEUS)

As the population ages, the growing prevalence of age-related diseases is creating substantial challenges for healthcare systems worldwide. Current therapeutic strategies often target individual diseases and decrease mortality without improving healthspan. The geroscience hypothesis suggests that targeting the ageing process itself could prevent, delay, or manage the severity of multiple age-related diseases concurrently, thereby improving overall healthspan and reducing healthcare burdens.

Emerging research highlights several interconnected hallmarks of aging, such as mitochondrial dysfunction, chronic inflammation, impaired autophagy, and immune dysregulation, as modifiable through targeted interventions. Precision geromedicine represents a paradigm shift in addressing these processes, combining baseline diagnostics with individualized treatment strategies that adapt over time based on patient response. This approach integrates lifestyle modifications, dietary supplements, and pharmacological agents to optimize physical, cognitive, and immune function across the lifespan .

This study aims to evaluate the effectiveness and feasibility of a personalized, multimodal precision geromedicine intervention targeting key hallmarks of aging. We hypothesize that an 8-week intervention combining lifestyle modification and targeted supplementation will improve biological and clinical markers of aging in middle-aged to older (50-80 years) adults.

Participants within this age range are chosen because they are more likely to encounter early declines in muscle, immune, and cognitive functions, while still being responsive to preventive measures. The criteria for inclusion concentrate on individuals scoring below the 75th percentile for normative values in VO₂peak and cognitive performance. This demographic presents an optimal opportunity for interventions aimed at prolonging healthspan and postponing functional decline.

Hypothesis

The multimodal precision geromedicine intervention will be feasible to conduct and effective in improving muscle, cognitive, and immune function, as well as other biological, clinical, and digital biomarkers of aging in middle aged to older adults.

Inclusion Criteria:

• Age 50-80 years (both male and female)
• Relatively healthy and in stable health condition
• Not engaged in regular resistance or aerobic training in the past 12 months (i.e., untrained)
• VO₂peak below the 75th percentile for age- and sex-specific norms
• Cognitive performance below 75th percentile on the NIH Toolbox Cognitive Function Battery
• Willing and able to comply with exercise and supplementation protocols
• English-literate (can read and understand English)
• Provides written informed consent
• Deemed to have mental capacity, as assessed by the Principal Investigator
• Are able to attend all research visits for screening and research data collection at MD11, Yong Loo Lin School of Medicine, National University of Singapore

Exclusion Criteria:

• Significant change in medication in the past 3 months
• History of major cardiovascular disease (e.g., coronary artery disease, heart failure, stroke)
• More than two unstable chronic conditions (e.g., hypertension, diabetes, osteoarthritis, COPD)
• Known allergies to soy, shellfish/seaweed, mushrooms, or supplement ingredients
• Participation in another interventional clinical trial
• Current use of any study-related supplement unless willing to stop
• Any medical, psychiatric, or cognitive condition deemed by the PI to jeopardise safety or compliance
• Pregnant or planning pregnancy during the study period
• Any conditions deemed by PI that jeopardize the safety or study compliance