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

Study Overview

• Status: Recruiting
• Conditions: Ageing
• Intervention / Treatment: Other: Sleep and dietary counseling; Other: Supervised exercise and exergaming program; Behavioral: Motivational interviewing; Dietary supplement: Whey protein; Dietary supplement: Creatine Monohydrate; Dietary supplement: Fucoidan; Dietary supplement: Urolithin A; Dietary supplement: Nicotinamide Mononucleotide (NMN); Dietary supplement: Multivitamin; Dietary supplement: Ergothioneine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ajla Hodzic Kuerec, MD, PhD; Phone Number: +65 91686091; Email: ahkuerec@nus.edu.sg
• Study Contact Backup: Name: Mazzarine Dotou, PhD; Phone Number: +65 87264704; Email: mazzarine@nus.edu.sg

Study Locations

• Singapore
  • Singapore
    • Singapore, Singapore, Singapore, 117597
      • Recruiting
      • MD11 Clinical Research Centre, #03-01, 10 Medical Drive, Singapore 117597
      • Contact: Ajla Hodzic Kuerec, MD, PhD; Phone Number: 87142730; Email: ahkuerec@nus.edu.sg
      • Contact: Mazzarine Dotou, PhD, MBA; Email: mazzarine@nus.edu.sg
      • Principal Investigator: Andrea Britta Maier, MD, PhD, FRACP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 Fundamental intervention; Participants receive a multimodal lifestyle intervention including sleep optimization, dietary counseling, supervised exercise with an exergaming component, motivational interviewing, and baseline nutritional supplementation.	Other: Sleep and dietary counseling; Sleep hygiene education and individualized dietary recommendations delivered throughout the intervention period.; Other: Supervised exercise and exergaming program; Supervised dual-task cognitive-physical training with an exergaming component conducted three times per week, 60 minutes per session.; Behavioral: Motivational interviewing; Structured motivational interviewing sessions aimed at improving adherence to lifestyle and supplementation interventions conducted two times throughout the study.; Dietary supplement: 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; Dietary supplement: 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; Dietary supplement: Fucoidan; Daily fucoidan supplementation (SIRT6Activator®, DoNotAge.org) at a dose of 2.4 g/day.
Experimental: 2 Augmented intervention; Participants receive the fundamental intervention and additional personalized supplements based on baseline muscle mass, cardiorespiratory fitness, and cognitive performance, with possible mid-study adjustment.	Other: Sleep and dietary counseling; Sleep hygiene education and individualized dietary recommendations delivered throughout the intervention period.; Other: Supervised exercise and exergaming program; Supervised dual-task cognitive-physical training with an exergaming component conducted three times per week, 60 minutes per session.; Behavioral: Motivational interviewing; Structured motivational interviewing sessions aimed at improving adherence to lifestyle and supplementation interventions conducted two times throughout the study.; Dietary supplement: 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; Dietary supplement: 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; Dietary supplement: Fucoidan; Daily fucoidan supplementation (SIRT6Activator®, DoNotAge.org) at a dose of 2.4 g/day.; Dietary supplement: Urolithin A; Participants below the 50th percentile for normative muscle mass receive urolithin A (StanYouth™ Urolithin A, Bonerge) at 250 mg/day.; Dietary supplement: Nicotinamide Mononucleotide (NMN); Participants below the 50th percentile for normative VO₂peak receive NMN (AbinoNutra® NMN, Abinopharm, Inc.) at 300 mg/day.; Dietary supplement: Multivitamin; Participants below the 50th percentile for normative cognitive performance receive a gender-specific multivitamin (Centrum), 1 tablet daily.; Dietary supplement: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in cardiorespiratory fitness (VO₂peak)	VO₂peak will be determined using standardized cardiopulmonary exercise testing on an electronically braked cycle ergometer	Baseline, Week 4, and Week 8
Change from baseline in muscle strength (one-repetition maximum (1RM))	Change from baseline in muscle strength assessed by one-repetition maximum (1RM) testing	Baseline, Week 4, and Week 8
Change from baseline in muscle mass (Ultrasound imaging)	Muscle thickness of the thigh will be assessed non-invasively using B-mode ultrasound with a linear array transducer.	Baseline, Week 4, and Week 8
Change from baseline in cognitive performance (NIH Toolbox Fluid Cognition Composite)	Change from baseline in cognitive performance assessed by the NIH Toolbox Fluid Cognition Composite score.	Baseline, Week 4, and Week 8
Change from baseline in immune function (CD4+: CD8+ ratio)	Change from baseline in immune status assessed by the CD4+:CD8+ T-cell ratio.	Baseline, Week 4, and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Circulating Cytokines, Chemokines, and Growth Factors	Change from baseline in circulating cytokines, chemokines, and growth factors. These will be quantified in plasma using enzyme-linked immunosorbent assays (ELISA) or multiplex immunoassays based on xMAP technology. Concentrations will be expressed in standard units (e.g., pg/mL)	Baseline, Week 4, and Week 8
Change from baseline in advanced glycation end-products	Change from baseline in tissue advanced glycation end-products (AGEs), assessed using skin autofluorescence.	Baseline, Week 4, and Week 8
Change from baseline in methylation levels	Genome-wide DNA methylation levels will be measured using Illumina BeadChips, which will be scanned on the iScan System. Methylation levels will be quantitatively determined from the fluorescence signals.	Baseline, Week 4, and Week 8
Change from baseline in blood multi-omics profiles	Blood-based multi-omics profiles, including proteomics and lipidomics, will be assessed using standard analytical platforms.	Baseline, Week 4, and Week 8
Change from baseline in gut microbiome composition and fuctional capacity	Gut microbiome composition and functional capacity will be characterized using short-read shotgun metagenomic sequencing of DNA extracted from stool samples. Changes from baseline to Week 8 will be assessed at the species and functional gene levels.	Baseline and Week 8
Change from Baseline in Body Composition (Fat and Lean Mass)	Body composition, including fat mass and lean mass, will be assessed using bioelectrical impedance analysis.	Baseline, Week 4, and Week 8
Change from Baseline in Arterial Stiffness (Carotid-Femoral Pulse Wave Velocity)	Carotid-femoral pulse wave velocity (cf-PWV) will be measured using applanation tonometry at the carotid artery combined with a thigh cuff.	Baseline, Week 4, and Week 8
Change from baseline in sleep quality	Sleep quality will be assessed using validated questionnaires, including the Pittsburgh Sleep Quality Index (PSQI) and the SATED questionnaire, as well as objective sleep metrics collected via the Oura Ring wearable device. Changes from baseline to each follow-up time point will be reported.	Baseline, Week 4, and Week 8
Change from baseline in skin color and elasticity	Skin color and elasticity will be assessed using a standardized colorimeter	Baseline, Week 4, and Week 8
Change from baseline in oral health indicators	Oral health status and mucosal condition will be assessed using validated questionnaires, including the Geriatric Oral Health Assessment Index (GOHAI) and the Modified CDC/AAP oral health questionnaires.	Baseline, Week 4, and Week 8
Change from baseline in reproductive health	Reproductive health will be assessed using validated questionnaires. For men, the Androgen Deficiency in Aging Males (ADAM) and Brief Sexual Function Inventory (BSFI) will be used; for women, the Female Sexual Function Index (FSFI) will be used.	Baseline, Week 4, and Week 8
Change from Baseline in Waist and Hip Circumferences	Waist and hip circumferences will be measured using a standardized measuring tape.	Baseline, Week 4, and Week 8
Change from Baseline in Blood Pressure (Systolic and Diastolic)	Brachial systolic and diastolic blood pressures will be measured using an automated cuff.	Baseline, Week 4, and Week 8
Change from baseline in Physical activity levels	Physical activity will be objectively measured using the Oura Ring wearable device, which passively tracks daily steps, activity intensity, and sleep duration throughout the intervention period.	Baseline, Week 4, and Week 8
Change from Baseline in Quality of Life	Quality of life will be assessed using the 36-Item Short Form Survey (SF-36) and EuroQol-5D-5L (EQ-5D).	Baseline, Week 4, and Week 8
Change from baseline in Psychological Well-being	Exhaustion will be evaluated using two items from the Center for Epidemiologic Studies Depression Scale (CES-D). Depression, anxiety, and stress levels will be measured using the 21-item Depression Anxiety and Stress Scale (DASS-21).	Baseline, Week 4, and Week 8
Change from baseline in wellness	Overall wellness will be assessed using a validated wellness questionnaire.	Baseline, Week 4, and Week 8
Change from baseline in food intake	Participants will record dietary intake using a 3-day food diary. Changes from baseline in nutrient and energy intake will be analyzed.	Baseline, Week 4, and Week 8
Change from Baseline in Grip Strength	Grip strength will be measured using a hand-held dynamometer (Jamar Plus+).	Baseline, Week 4, and Week 8
Change from Baseline in Standard Clinical Blood Biomarkers	Standard clinical blood tests, including hematology, liver and renal function profiles, lipid profile, glucose, HbA1c, insulin, and high-sensitivity C-reactive protein (hs-CRP), will be conducted by an accredited clinical laboratory.	Baseline, Week 4, and Week 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study participation and retention rates	Participation rate defined as the percentage of eligible participants enrolled, and dropout rate defined as the percentage of participants who discontinue the study and reasons for dropout.	8 weeks
Adherence to sleep intervention	Adherence to the sleep intervention expressed as the number and percentage of nights with ≥7 hours of sleep, recorded using a wearable device.	8 weeks
Adherence to fundamental supplementation	Adherence to whey protein, creatine, and fucoidan supplementation assessed as the number and percentage of prescribed doses taken, verified by counting and weighing returned supplement bottles.	8 weeks
Adherence to augmented supplementation	Adherence to urolithin A, NMN, multivitamin, ergothioneine, or additional fucoidan assessed as the number and percentage of prescribed doses taken, verified by counting and weighing returned supplement bottles.	8 weeks
Adherence to exercise and exergaming intervention	Adherence to the exercise intervention expressed as the number and percentage of aerobic training, strength training, and exergaming sessions attended, recorded by study staff.	8 weeks

Collaborators and Investigators

• Sponsor: National University of Singapore
• Collaborators: Abinopharm, Inc; DoNotAge.org; Xprize Foundation
• Investigators: Principal Investigator: Prof. Andrea Britta Maier, MD, PhD, National University of Singapore

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2025
• Primary Completion (Actual): February 23, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: February 28, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: February 28, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Aging; Fucoidan; DNA methylation; Creatine; Multivitamin; Geroscience; NMN; Healthspan; Urolithin A; Ergothioneine; Whey Protein supplementation; Epigenetic aging clock
• Additional Relevant MeSH Terms: Health Care Quality, Access, and Evaluation; Amino Acids, Peptides, and Proteins; Proteins; Musculoskeletal and Neural Physiological Phenomena; Sulfur Compounds; Organic Chemicals; Investigative Techniques; Epidemiologic Methods; Nucleic Acids, Nucleotides, and Nucleosides; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Amino Acids; Health Services; Health Care Facilities Workforce and Services; Behavioral Disciplines and Activities; Dairy Products; Directive Counseling; Counseling; Mental Health Services; Epidemiologic Measurements; Amino Acids, Cyclic; Guanidines; Amidines; Ribonucleotides; Nucleotides; Milk; Sulfhydryl Compounds; Nervous System Physiological Phenomena; Dietary Proteins; Milk Proteins; Animal Proteins, Dietary; Whey; Histidine; Ergothioneine; Motivational Interviewing; 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; Nicotinamide Mononucleotide; Nutrition Assessment; Geritol; Creatine; Sleep; Whey Proteins; fucoidan
• Other Study ID Numbers: NUS-IRB-2025-393

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the primary, secondary and other outcome measures reported in this study, will be made available on request. Data will be fully de-identified and will not include direct identifiers. Raw multi-omics data (e.g., DNA methylation, proteomics, lipidomics, microbiome sequencing) may be shared in processed or aggregated form, as appropriate, to minimize re-identification risk.
• IPD Sharing Time Frame: IPD and supporting information will become available after study completion and publication of the main findings, with the end date to be determined.
• IPD Sharing Access Criteria: Access to de-identified IPD will be provided upon reasonable request to qualified researchers with a methodologically sound proposal and appropriate ethical approval. Requests will be reviewed by the study investigators and data will be shared under a data use agreement specifying permitted uses, data security requirements, and restrictions on re-identification.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No