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Elevated Circulating Ceramides 18:0 and 24:1 as a Risk Factor for Sarcopenia: In Vitro, Animal, and Clinical

So Jeong Park1, Ji Yeon Baek2, Shibo Wei3

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Elevated C18:0 and C24:1 ceramides are linked to sarcopenia, causing muscle atrophy via oxidative stress. Modulating ceramide metabolism may offer new therapeutic strategies for age-related muscle decline.

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Area of Science:

  • Lipid metabolism and aging research
  • Skeletal muscle physiology
  • Gerontology and geriatric medicine

Background:

  • Ceramides are bioactive lipids associated with aging, metabolic dysfunction, and musculoskeletal decline.
  • Specific ceramides, C18:0 and C24:1, are implicated in sarcopenia, but their precise role in muscle degeneration is unclear.

Purpose of the Study:

  • To investigate the role of C18:0 and C24:1 ceramides in muscle atrophy and sarcopenia.
  • To explore their potential as biomarkers and therapeutic targets for age-related muscle loss.

Main Methods:

  • In vitro studies using C2C12 and primary myoblasts treated with C18:0 or C24:1 ceramides.
  • In vivo studies involving intraperitoneal injections of ceramides in C57BL/6 mice.
  • Clinical analysis of serum ceramide levels in a cohort of older adults with and without sarcopenia.

Main Results:

  • Both ceramides impaired myogenesis in vitro via oxidative stress and downregulated myogenic markers.
  • Ceramide administration in mice led to reduced muscle fiber size and impaired muscle function.
  • Higher serum levels of C18:0 and C24:1 ceramides were significantly associated with sarcopenia in older adults, increasing the risk.

Conclusions:

  • Circulating C18:0 and C24:1 ceramides are linked to sarcopenia and promote muscle atrophy through oxidative stress.
  • These ceramides show potential as minimally invasive biomarkers for sarcopenia.
  • Targeting ceramide metabolism could provide novel therapeutic approaches for age-related muscle decline.