NCT07500649

Project SIRT6 Activator

SIRT6 Activation to Improve Biological Age Measured by GrimAge in Pre-frail, Middle-aged to Older Men: a Randomized Controlled Trial

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: National University of Singapore · Academic / Other
• Sex: Male
• Age: 50 Years – 80 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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.

Conditions

• Aging

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Fucoidan	Eligible participants will be randomized to receive SIRT6 Activator (fucoidan) or Placebo for 6 months.
DIETARY_SUPPLEMENT	Placebo	Eligible participants will be randomized to receive SIRT6 Activator (fucoidan) or Placebo for 6 months.

Timeline

• Start date: 2025-07-01
• Primary completion: 2027-03-31
• Completion: 2027-12-31
• First posted: 2026-03-30
• Last updated: 2026-03-30

Locations

2 sites across 1 country: Singapore