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Fucoidans are senotherapeutics that enhance SIRT6-dependent DNA repair

Paul Robbins1, Lei Zhang1, Osama Elsallabi2

  • 1University of Minnesota.

Research Square
|June 12, 2025
PubMed

Insights

Fucoidans from seaweed show promise as senotherapeutics, reducing aging cells and improving healthspan in mice. This natural compound enhances DNA repair mechanisms, offering a new avenue for age-related disease treatment.

Area of Science:

  • Cellular senescence
  • Aging research
  • Natural product therapeutics

Background:

  • Aging is characterized by senescent cells (SnCs) accumulation, leading to tissue dysfunction and age-related diseases.
  • Senotherapeutics, including senolytics and senomorphics, are emerging as potential interventions to combat aging.
  • Identifying novel compounds with senotherapeutic properties is crucial for extending healthspan.

Purpose of the Study:

  • To identify novel senotherapeutics from natural sources.
  • To investigate the senomorphic potential of fucoidans, particularly fucoidan from Fucus vesiculosus (Fucoidan-FV).
  • To elucidate the molecular mechanisms underlying Fucoidan-FV's effects on senescence and DNA repair.

Main Methods:

  • Phenotypic-based senescent cell screening assay to identify senotherapeutics.
  • In vitro testing of Fucoidan-FV on different types of senescent cells (SnCs).
  • In vivo studies in aged mice and a mouse model of accelerated aging to assess healthspan and senescence.
  • Analysis of SIRT6 activity, DNA repair pathways, and gene expression profiles (inflammation, Wnt signaling, ECM remodeling).

Main Results:

  • Fucoidan-FV demonstrated potent senomorphic activity in various SnCs.
  • Treatment with Fucoidan-FV reduced senescence in multiple tissues of aged mice and extended healthspan in an accelerated aging model.
  • Fucoidan-FV enhanced SIRT6 activity, leading to improved DNA repair and reduced senescence via SIRT6-dependent pathways.
  • Fucoidan-FV modulated gene expression in SnCs, downregulating inflammatory and Wnt signaling pathways while upregulating DNA repair genes.

Conclusions:

  • Fucoidans, particularly Fucoidan-FV, are identified as novel senotherapeutics with significant senomorphic effects.
  • Fucoidan-FV extends healthspan and mitigates aging phenotypes in mice, partly through enhancing SIRT6-mediated DNA repair.
  • These findings highlight the translational potential of fucoidans for treating age-related diseases and promoting healthy aging.
Keywords:
DNA repairNHEJSIRT6agingfucoidanhealthspanseaweedsenescencesenolyticsenomorphicsenotherapeutic

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