Drug Screening Implicates Chondroitin Sulfate as a Potential Longevity Pill

Abstract

Discovering compounds that promote health during aging (“geroprotectors”) is key to the retardation of age-related pathologies and the prevention of chronic age-related diseases. In in-silico and model organisms’ lifespan screens, chondroitin sulfate has emerged as a geroprotective compound. Chondroitin sulfate is a glycosaminoglycan attached to extracellular matrix proteins and is naturally produced by our body. Oral supplementation of chondroitin sulfate shows a high tolerance in humans, preferable pharmacokinetics, a positive correlation with healthy human longevity, and efficacy in deceleration of age-related diseases in randomized clinical trials. We have recently shown that chondroitin sulfate supplementation increases the lifespan of C. elegans. Thus, chondroitin sulfate holds the potential to become a geroprotective strategy to promote health during human aging. This review discusses the two major potential mechanisms of action, extracellular matrix homeostasis and inhibition of inflammation, that counteract age-related pathologies upon chondroitin sulfate supplementation.

Mechanotransduction coordinates extracellular matrix protein homeostasis promoting longevity inC. elegans

“…The longer this adulthood growth phase is, the longer-lived is an individual C. elegans (Hulme et al, 2010). To test whether this correlation is associated with prolonged production of the pattern I collagens, we used transgenic animals expressing GFP driven by the collagen col-144 promoter, whose expression gradually declines during aging (Ewald, 2021; Statzer et al, 2021a), and split this isogenic population grown in the same environment into high expression and low expression of P col-144 ::GFP transgenic animals at day 5 of adulthood. Animals expressing higher levels of P col-144 ::GFP at day 5 of adulthood lived longer than their genetically identical siblings with lower levels of col- 144 -driven GFP expressed (Figure 3F, Supplementary Table7), demonstrating that prolonged pattern I collagen expression is associated with longevity.…”

Mucopolysaccharidosis Type IVA: Extracellular Matrix Biomarkers in Cardiovascular Disease

“…CRP is known to modulate innate immune response, promote platelet activation, vascular remodeling, and angiogenesis ( 89 ). Recent studies showed that CS intake is associated with a reduction in CRP concentration in blood, indicating decrease in inflammation ( 90 – 92 ). These findings, along with the significantly lower CRP levels in Morquio A patients found in this study, open a new direction in this field to gain insights in the understanding of vascular endothelial glycocalyx dysregulation in this patient population.…”

Low Energy Blue Pulsed Light‐Activated Injectable Materials for Restoring Thinning Corneas

“…Further, the use of polysaccharides in our formulation instead of animal-derived proteins should reduce the immunogenic reaction risk and cost of raw materials. [20][21][22] Researchers typically apply biomaterials to cornea defects and crosslink in situ to form a tissue-adherent gel. Chemical crosslinking strategies specifically involving Nhydroxysuccinimide reactions and strain-promoted azide-alkyne cycloaddition have shown great promise in cornea repair.…”

“…Further, the use of polysaccharides in our formulation instead of animal‐derived proteins should reduce the immunogenic reaction risk and cost of raw materials. [ 20–22 ]…”