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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Enrollment
20
Sleep hygiene education and individualized dietary recommendations delivered throughout the intervention period.
Supervised dual-task cognitive-physical training with an exergaming component conducted three times per week, 60 minutes per session.
Structured motivational interviewing sessions aimed at improving adherence to lifestyle and supplementation interventions conducted two times throughout the study.
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
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
Daily fucoidan supplementation (SIRT6Activator®, DoNotAge.org) at a dose of 2.4 g/day.
Participants below the 50th percentile for normative muscle mass receive urolithin A (StanYouth™ Urolithin A, Bonerge) at 250 mg/day.
Participants below the 50th percentile for normative VO₂peak receive NMN (AbinoNutra® NMN, Abinopharm, Inc.) at 300 mg/day.
Participants below the 50th percentile for normative cognitive performance receive a gender-specific multivitamin (Centrum), 1 tablet daily.
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.
MD11 Clinical Research Centre, #03-01, 10 Medical Drive, Singapore 117597
Singapore, Singapore, Singapore
RECRUITINGChange from baseline in cardiorespiratory fitness (VO₂peak)
VO₂peak will be determined using standardized cardiopulmonary exercise testing on an electronically braked cycle ergometer
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 4, and Week 8
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)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: Baseline, Week 4, and Week 8
Change from baseline in wellness
Overall wellness will be assessed using a validated wellness questionnaire.
Time frame: 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.
Time frame: Baseline, Week 4, and Week 8
Change from Baseline in Grip Strength
Grip strength will be measured using a hand-held dynamometer (Jamar Plus+).
Time frame: 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.
Time frame: Baseline, Week 4, and Week 8
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.