Overview
National multicentric registry of a cohort of patient with suffering parietal endometriosis, carried out by a multidisciplinary radiosurgery team
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.
Eligibility
Inclusion Criteria:
- Presence of parietal endometriosis: with suggestive clinical and imaging criteria (MRI and ultrasound)
- Symptomatic parietal endometriosis (VAS \> 3 OR bothersome bleeding OR reported impact on quality of life)
Exclusion Criteria:
- Endometriosis not affecting the anterior wall of the abdomen (as deep pelvic muscle: ilio-psoas, obturators, perineal, ischio-anal fossa)
- Minor patient (\< 18 years)
- Pregnant patient at any trimester
- Patient with hemostasis disorders (constitutional or acquired)
- Patient with systemic infection or localized scar infection upon inclusion.
- Patient with contraindications to MRI
- Female patient with a planned medical or surgical procedure for the duration of the study that may interfere with the proper conduct of the study.
- Patient unable to understand the information provided
- Patient who is not affiliated to the social security system
- Patient under curatorship or tutorship
- Patient with a nodule of primary or secondary malignant tumor originticoagulant medication; 4. Consuming seaweed more than 3 times a week; 5. Having hairiness, moles, tattoos, scars, irritated skin, etc. on the face which could influence the investigation; 6. Having used within the 3 past weeks for more than 3 consecutive days any systemic or topical drugs related to antibiotics or having planned to use these treatments during the study; 7. Having a positive serology for HIV, HEPATITIS B, HEPATITIS C\*
\*Subjects will undergo a serology test, which will be conducted at baseline and at the end of the intervention visit. Only for subjects who accepted to undergo skin microbiopsy sampling; 8. Subject with any contra-indication for skin microbiopsies:
- hypersensitivity or any serious reaction to local anesthesia; (lidocaine/prilocaine), local antibiotics, and antiseptics,
- with inherited or acquired hemostasis disorders,
- having had any treatment which may affect the blood coagulation and hemostasis (anti-coagulant medications…),
- having a history of wound healing defects (hypertrophic scars, keloids…).
