The global ageing population is increasingly affected by age-related diseases, which are challenging healthcare systems. Current treatments often extend lifespan without improving healthspan. The geroscience hypothesis suggests that targeting the ageing process could prevent or delay multiple diseases, enhancing healthspan. Fucoidan, a sulfated polysaccharide from brown macroalgae, is a safe dietary supplement with Sirtuin-6 (SIRT6) activating properties, which are linked to longevity. Clinical studies have shown that it reduces inflammatory markers associated with biological aging and frailty and influences DNA methylation in vitro and in vivo; however, its effects on human DNA methylation remain unknown.
Ageing is driven by several interconnected mechanisms, including deoxyribonucleic acid (DNA) damage, mitochondrial dysfunction, depletion of nicotinamide adenine dinucleotide (NAD+) levels, impaired autophagy, stem cell exhaustion, chronic inflammation, loss of protein homeostasis, deregulated nutrient sensing, altered intercellular communication, and microbiome imbalance. Sirtuin 6 (SIRT6) an NAD+ dependent deacetylase and ADP-ribosyl-transferase, has emerged as a pivotal factor in the regulation of several of these mechanisms, including DNA repair, metabolism, and inflammation. Long-lived species have higher SIRT6 activity. Potent and safe SIRT6 activators have the potential to extend human lifespan and healthspan. Fucoidan, a polymer of L-fucose and L-fucose-4-sulfate derived from brown macroalgae is available as a dietary supplement, safe for human consumption, and rarely causes irritation. Fucoidan exhibits dose-dependent SIRT6-stimulating activity and extends lifespan in model organisms. Inflammation is associated with higher biological age and poor health outcomes, including frailty. In an open-label single-arm clinical study where 400 ml (10mg/ml) fucoidan was administered to 20 cancer patients (mean age 58.9 years) reported a decrease in the interleukin (IL) levels (IL-6, IL-1-beta) and tumour necrosis factor (TNF)-alpha, after 2 weeks compared to baseline levels. In addition, studies found that fucoidan modulates DNA methylation (DNAm) in vitro and in vivo and play a role of inhibiting carcinogenesis. Currently, there is no data about the effect of fucoidan on DNAm in humans. Therefore, this study will investigate the effects of a SIRT6 activator, compared to a placebo, on DNAm assessed by GrimAge in 60 prefrail, middle-aged to older (50-80 years) healthy males. The aim is to evaluate the geroprotective effect of a SIRT6 activator and determine whether it can modulate biological pathways of ageing. The investigators hypothesize that supplementation with a SIRT6 activator (2.4 g/day/6 months) will decrease DNAm as assessed by GrimAge in prefrail, middle-aged to older (50-80 years), males and improve biological (inflammatory, glycans) and clinical markers of ageing (frailty, quality of life, sleep, cognitive, body composition, muscular, cardiovascular, and reproductive and skin ageing). Study objectives: to assess the effect of supplementation with a SIRT6 activator (2.4 g/day/6 months) on biological (epigenetic inflammatory, glycans) and clinical markers of ageing (frailty, quality of life, sleep, cognitive, body composition, muscular, cardiovascular, reproductive and skin ageing) compared to placebo in 60 prefrail, middle-aged to older (50-80 years), males.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
QUADRUPLE
Enrollment
60
Yong Loo Lin School of Medicine, National University of Singapore
Singapore, Singapore, Singapore
RECRUITINGNUS Academy for Healthy Longevity, Level 6, MD 11, 10 Medical Dr, Yong Loo Lin School of Medicine, National University of Singapore
Singapore, Singapore
NOT_YET_RECRUITINGChange in blood DNA methylation status, years
DNA methylation aging clock
Time frame: from baseline to end of intervention (6 months)
Change in blood inflammatory markers (pg/mL)
comparison of inflammatory markers: IL-10, IFN-γ，IL-17, TNF-a, IL-6，CXCL9 (pg/mL) at baseline, interim and end-of-trial
Time frame: from baseline to end of intervention (6 months)
Body Mass Index (BMI) change
comparison of BMI at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Waist-to-hip ratio change
comparison of waist-to-hip ratio at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Body fat mass (kg) change
comparison of body fat mass at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Skeletal muscle mass (kg) change
comparison of skeletal muscle mass at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Percentage body fat (%) change
comparison of percentage body fat at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Systolic blood pressure (mm Hg) change
comparison of systolic blood pressure at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Diastolic blood pressure (mm Hg) change
comparison of diastolic blood pressure at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Pulse rate (BPM) change
comparison of pulse rate at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Skin elasticity (mm/time) change
comparison of skin elasticity measured by he resistance of the skin to the negative pressure (firmness) and its ability to return into its original position (elasticity) displayed as curves (penetration depth in mm/time) at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Skin colour (L* a* b*) change
comparison of skin colour measured using automatic calculation of ITA (Individual Typology Angle) that uses CIE L\* a\* b\* values to classify 6 skin colours from very light to dark at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Skin autofluorescence (au) change
comparison of skin autofluorescence levels calculated by dividing the mean value of the emitted light intensity per nm between 420 and 600 nm by the mean value of the excitation light intensity per nm between 300 and 420 nm, expressed in arbitrary units (AU) at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Skin evaluation: microbiopsies for proteomics
Time frame: from baseline to end of intervention (6 months)
Complete blood count: lymphocytes_countm, neutrophils_count, monocyte_count, basophil_count, eosinphil_count, WBC_count,PLT_count (*10^9/L)
comparison of blood count at baseline, interim and end-of-trial.
Time frame: from baseline to end of intervention (6 months)
Change in cognition (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Test)
comparison of cognition at baseline, interim and end of trial. A RBANS result range from 40-160, the higher scale indicates the better congnition function.
Time frame: from baseline to end of intervention (6 months)
Change in Physical Activity (Minnesota Leisure Time Activity Questionnaire)
comparison of physical activity at baseline, interim and end of trial. The higher the value (energy expenditure or time), the higher the level of physical activity during leisure time.
Time frame: from baseline to end of intervention (6 months)
Change in Exhaustion [Center for Epidemiologic Studies Depression Scale (CES-D)]
CES-D scale range from 0-60. The higher the score, the more severe the depressive symptoms. comparison of exhaustion at baseline, interim and end of trial.
Time frame: from baseline to end of intervention (6 months)
Change in dietary intake (3-day Food Record)
comparison of dietary intake at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Change in quality of life 36-Item Short Form Survey (SF-36)
comparison of quality of life 36-Item Short Form Survey (SF-36) at baseline, interim and end of trial. SF-36\_overall range from 0-100, the larger scale indicates the better quality of life.
Time frame: from baseline to end of intervention (6 months)
Change in Depression, anxiety and/ or stress levels [Depression Anxiety and Stress Scale (21 items) (DASS-21)]
DASS-21 scale ranges from 0-21. The higher the score, the more severe the symptoms in that dimension are. comparison of depression, anxiety and/ or stress levels at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Change in Reproductive health [Androgen Deficiency in Aging Males (ADAM) questionnaire]
Androgen Deficiency in Aging Males (ADAM) questionnaire scale ranges from 0-10. A "Positive" result indicates a high likelihood of androgen deficiency, warranting further clinical evaluation (e.g., testosterone testing). comparison of reproductive health at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Change in sleep quality (modified Pittsburgh Sleep Quality Questionnaire)
modified Pittsburgh Sleep Quality Questionnaire scale ranges from 0-21. Higher total scores indicate worse sleep quality. comparison of sleep quality at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Change in handgrip strength change (kg)
comparison of handgrip strength at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Change in 8-RM leg extension change (kg)
comparison of 8-RM leg extension at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Carotid-femoral Pulse Wave Velocity change
comparison of carotid-femoral pulse wave velocity at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Central Blood pressure change
comparison of central Blood pressure at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Change in blood inflammatory markers:hs-CRP (mg/mL)
Time frame: basline, 3 months, and 6 months
Change in quality of life: EuroQol-D5-5L (EQ-5D)
A 5-digit code describing a health state. This code is then converted to a single index number using a country-specific value set (a formula based on public preferences). comparison of quality of life of EQ-5D at baseline, interim and end of trial
Time frame: from baseline to end of intervention (6 months)
Skin micobiopsies for microbiomics.
Time frame: Time Frame: from baseline to the end of the trial (6 months)
Skin micobiopsies: Transcriptomics
Time frame: from baseline to the end of ths study (6 months)
skin microbiopsies evaluation: DNA methylation
Time frame: from baseline to the end of this study (6 months)
Complete blood count: red blood cell_count (*10^12/L)
comparison of blood count at baseline, interim and end-of-trial.
Time frame: from baseline to end of intervention (6 months)
Complete blood count: Hemoglobulin (*g/L)
comparison of blood count at baseline, interim and end-of-trial.
Time frame: Time Frame: from baseline to end of intervention (6 months)
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