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 .
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
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
Sequential
Sleep and dietary counseling
Other interventionSleep hygiene education and individualized dietary recommendations delivered throughout the intervention period.
Supervised exercise and exergaming program
Other interventionSupervised dual-task cognitive-physical training with an exergaming component conducted three times per week, 60 minutes per session.
Motivational interviewing
BehavioralStructured motivational interviewing sessions aimed at improving adherence to lifestyle and supplementation interventions conducted two times throughout the study.
Whey protein
Dietary supplementDaily 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
Creatine Monohydrate
Dietary supplementDaily 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
Fucoidan
Dietary supplementDaily fucoidan supplementation (SIRT6Activator®, DoNotAge.org) at a dose of 2.4 g/day.
Urolithin A
Dietary supplementParticipants below the 50th percentile for normative muscle mass receive urolithin A (StanYouth™ Urolithin A, Bonerge) at 250 mg/day.
Nicotinamide Mononucleotide (NMN)
Dietary supplementParticipants below the 50th percentile for normative VO₂peak receive NMN (AbinoNutra® NMN, Abinopharm, Inc.) at 300 mg/day.
Multivitamin
Dietary supplementParticipants below the 50th percentile for normative cognitive performance receive a gender-specific multivitamin (Centrum), 1 tablet daily.
Ergothioneine
Dietary supplementAt 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.
Change from baseline in cardiorespiratory fitness (VO₂peak)
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))
Change from baseline in muscle strength assessed by one-repetition maximum (1RM) testing
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.
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.
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)
Change from baseline in advanced glycation end-products
Change from baseline in tissue advanced glycation end-products (AGEs), assessed using skin autofluorescence.
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.
Change from baseline in blood multi-omics profiles
Blood-based multi-omics profiles, including proteomics and lipidomics, will be assessed using standard analytical platforms.
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.
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.
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.
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.
Click on the lead sponsor to view all of their trials.
National University of Singapore
Lead sponsor
Xprize Foundation
Collaborator
Abinopharm, Inc
Collaborator
DoNotAge.org
Collaborator
