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

Обзор

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 .

Подробное описание

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.

Вмешательства

• Другое Sleep and dietary counseling
  Sleep hygiene education and individualized dietary recommendations delivered throughout the intervention period.
• Другое Supervised exercise and exergaming program
  Supervised dual-task cognitive-physical training with an exergaming component conducted three times per week, 60 minutes per session.
• Поведенческое Motivational interviewing
  Structured motivational interviewing sessions aimed at improving adherence to lifestyle and supplementation interventions conducted two times throughout the study.
• Пищевая добавка Whey protein
  Daily whey protein supplementation (GOLD STANDARD 100% ISOLATE, Optimum Nutrition) provided using a standard 30 g scoop (\~25 g protein). Dosage based on body weight: 40-59 kg: 1 scoop/day 60-89 kg: 1.5 scoops/day ≥90 kg: 2 scoops/day
• Пищевая добавка Creatine Monohydrate
  Daily creatine supplementation (Micronized Creatine Monohydrate, Optimum Nutrition; 1.25 g per capsule). Dosage based on body weight: 40-59 kg: 4 capsules/day 60-89 kg: 6 capsules/day ≥90 kg: 8 capsules/day
• Пищевая добавка Fucoidan
  Daily fucoidan supplementation (SIRT6Activator®, DoNotAge.org) at a dose of 2.4 g/day.
• Пищевая добавка Urolithin A
  Participants below the 50th percentile for normative muscle mass receive urolithin A (StanYouth™ Urolithin A, Bonerge) at 250 mg/day.
• Пищевая добавка Nicotinamide Mononucleotide (NMN)
  Participants below the 50th percentile for normative VO₂peak receive NMN (AbinoNutra® NMN, Abinopharm, Inc.) at 300 mg/day.
• Пищевая добавка Multivitamin
  Participants below the 50th percentile for normative cognitive performance receive a gender-specific multivitamin (Centrum), 1 tablet daily.
• Пищевая добавка Ergothioneine
  At the midpoint of the intervention (1 month), participants may receive ergothioneine (Dr.Ergo® L-ergothioneine) at 25 mg three times per week based on individual response.

Первичные конечные точки

• Change from baseline in cardiorespiratory fitness (VO₂peak) [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in muscle strength (one-repetition maximum (1RM)) [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in muscle mass (Ultrasound imaging) [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in cognitive performance (NIH Toolbox Fluid Cognition Composite) [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in immune function (CD4+: CD8+ ratio) [Срок оценки: Baseline, Week 4, and Week 8]

Вторичные конечные точки (12)

• Change from Baseline in Circulating Cytokines, Chemokines, and Growth Factors [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in advanced glycation end-products [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in methylation levels [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in blood multi-omics profiles [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in gut microbiome composition and fuctional capacity [Срок оценки: Baseline and Week 8]
• Change from Baseline in Body Composition (Fat and Lean Mass) [Срок оценки: Baseline, Week 4, and Week 8]
• Change from Baseline in Arterial Stiffness (Carotid-Femoral Pulse Wave Velocity) [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in sleep quality [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in skin color and elasticity [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in oral health indicators [Срок оценки: Baseline, Week 4, and Week 8]
• Change from baseline in reproductive health [Срок оценки: Baseline, Week 4, and Week 8]
• Change from Baseline in Waist and Hip Circumferences [Срок оценки: Baseline, Week 4, and Week 8]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Организация здравоохранения

Центры проведения

Сингапур · 1 центр

• MD11 Clinical Research Centre, #03-01, 10 Medical Drive, Singapore 117597 — Singapore

Идентификаторы

NCT: NCT07451496 · NUS-IRB-2025-393

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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