Ageing
Conditions
Keywords
Whey Protein supplementation, Creatine, Fucoidan, NMN, Multivitamin, Ergothioneine, Urolithin A, Aging, Geroscience, DNA methylation, Healthspan, Epigenetic aging clock
Brief summary
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 .
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.
Interventions
OTHERSleep and dietary counseling
Sleep hygiene education and individualized dietary recommendations delivered throughout the intervention period.
OTHERSupervised exercise and exergaming program
Supervised dual-task cognitive-physical training with an exergaming component conducted three times per week, 60 minutes per session.
BEHAVIORALMotivational interviewing
Structured motivational interviewing sessions aimed at improving adherence to lifestyle and supplementation interventions conducted two times throughout the study.
DIETARY_SUPPLEMENTWhey 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_SUPPLEMENTCreatine 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_SUPPLEMENTFucoidan
Daily fucoidan supplementation (SIRT6Activator®, DoNotAge.org) at a dose of 2.4 g/day.
DIETARY_SUPPLEMENTUrolithin A
Participants below the 50th percentile for normative muscle mass receive urolithin A (StanYouth™ Urolithin A, Bonerge) at 250 mg/day.
DIETARY_SUPPLEMENTNicotinamide Mononucleotide (NMN)
Participants below the 50th percentile for normative VO₂peak receive NMN (AbinoNutra® NMN, Abinopharm, Inc.) at 300 mg/day.
DIETARY_SUPPLEMENTMultivitamin
Participants below the 50th percentile for normative cognitive performance receive a gender-specific multivitamin (Centrum), 1 tablet daily.
DIETARY_SUPPLEMENTErgothioneine
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.
Sponsors
National University of Singapore
Xprize Foundation
Abinopharm, Inc
DoNotAge.org
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
This is an open-label, single arm interventional feasibility study in which 20 participants (aged 50 to 80 years) will receive an 8-week multimodal precision geromedicine intervention.
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in muscle mass (Ultrasound imaging) | Baseline, Week 4, and Week 8 | Muscle thickness of the thigh will be assessed non-invasively using B-mode ultrasound with a linear array transducer. |
| Change from baseline in cognitive performance (NIH Toolbox Fluid Cognition Composite) | Baseline, Week 4, and Week 8 | Change from baseline in cognitive performance assessed by the NIH Toolbox Fluid Cognition Composite score. |
| Change from baseline in immune function (CD4+: CD8+ ratio) | Baseline, Week 4, and Week 8 | Change from baseline in immune status assessed by the CD4+:CD8+ T-cell ratio. |
| Change from baseline in cardiorespiratory fitness (VO₂peak) | Baseline, Week 4, and Week 8 | VO₂peak will be determined using standardized cardiopulmonary exercise testing on an electronically braked cycle ergometer |
| Change from baseline in muscle strength (one-repetition maximum (1RM)) | Baseline, Week 4, and Week 8 | Change from baseline in muscle strength assessed by one-repetition maximum (1RM) testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Circulating Cytokines, Chemokines, and Growth Factors | Baseline, Week 4, and Week 8 | 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) |
| Change from baseline in advanced glycation end-products | Baseline, Week 4, and Week 8 | Change from baseline in tissue advanced glycation end-products (AGEs), assessed using skin autofluorescence. |
| Change from baseline in methylation levels | Baseline, Week 4, and Week 8 | 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. |
| Change from baseline in blood multi-omics profiles | Baseline, Week 4, and Week 8 | Blood-based multi-omics profiles, including proteomics and lipidomics, will be assessed using standard analytical platforms. |
| Change from baseline in gut microbiome composition and fuctional capacity | Baseline and Week 8 | 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. |
| Change from Baseline in Body Composition (Fat and Lean Mass) | Baseline, Week 4, and Week 8 | Body composition, including fat mass and lean mass, will be assessed using bioelectrical impedance analysis. |
| Change from Baseline in Arterial Stiffness (Carotid-Femoral Pulse Wave Velocity) | Baseline, Week 4, and Week 8 | Carotid-femoral pulse wave velocity (cf-PWV) will be measured using applanation tonometry at the carotid artery combined with a thigh cuff. |
| Change from baseline in sleep quality | Baseline, Week 4, and Week 8 | 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. |
| Change from baseline in skin color and elasticity | Baseline, Week 4, and Week 8 | Skin color and elasticity will be assessed using a standardized colorimeter |
| Change from baseline in oral health indicators | Baseline, Week 4, and Week 8 | 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. |
| Change from baseline in reproductive health | Baseline, Week 4, and Week 8 | 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. |
| Change from Baseline in Waist and Hip Circumferences | Baseline, Week 4, and Week 8 | Waist and hip circumferences will be measured using a standardized measuring tape. |
| Change from Baseline in Blood Pressure (Systolic and Diastolic) | Baseline, Week 4, and Week 8 | Brachial systolic and diastolic blood pressures will be measured using an automated cuff. |
| Change from baseline in Physical activity levels | Baseline, Week 4, and Week 8 | 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. |
| Change from Baseline in Quality of Life | Baseline, Week 4, and Week 8 | Quality of life will be assessed using the 36-Item Short Form Survey (SF-36) and EuroQol-5D-5L (EQ-5D). |
| Change from baseline in Psychological Well-being | Baseline, Week 4, and Week 8 | 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). |
| Change from baseline in wellness | Baseline, Week 4, and Week 8 | Overall wellness will be assessed using a validated wellness questionnaire. |
| Change from baseline in food intake | Baseline, Week 4, and Week 8 | Participants will record dietary intake using a 3-day food diary. Changes from baseline in nutrient and energy intake will be analyzed. |
| Change from Baseline in Grip Strength | Baseline, Week 4, and Week 8 | Grip strength will be measured using a hand-held dynamometer (Jamar Plus+). |
| Change from Baseline in Standard Clinical Blood Biomarkers | Baseline, Week 4, and Week 8 | 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. |
Countries
Singapore
Contacts
CONTACTAjla Hodzic Kuerec, MD, PhD
CONTACTMazzarine Dotou, PhD
PRINCIPAL_INVESTIGATORProf. Andrea Britta Maier, MD, PhD
National University of Singapore
Outcome results
None listed