The induction of the fibroblast extracellular senescence metabolome is a dynamic process

Emma N L James1, Mark H Bennett2, E Kenneth Parkinson3

  • 1Centre for Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London, E1 2AD, UK.

Scientific Reports
|August 16, 2018
PubMed

Insights

Cellular senescence, linked to DNA damage, can be identified by specific extracellular metabolites. These metabolic signatures offer new non-invasive biomarkers for aging and senescence.

Area of Science:

  • Gerontology
  • Cell Biology
  • Metabolomics

Background:

  • Cellular senescence, characterized by irreparable DNA double-strand breaks (IrrDSBs), is a hallmark of aging.
  • Senescent cell removal improves age-related diseases, but non-invasive biomarkers are needed for clinical translation.
  • Extracellular senescence metabolome (ESM) comprises serum metabolites indicating chronological age and accumulating independently of cell cycle arrest.

Purpose of the Study:

  • To characterize non-invasive biomarkers for senescent cells.
  • To investigate the dynamic changes in the extracellular senescence metabolome (ESM) associated with aging and senescence.
  • To identify novel ESM metabolites linked to chronological aging and cellular senescence.

Main Methods:

  • Unbiased metabolomic screening of ESM from fibroblasts with irreparable DNA double-strand breaks (IrrDSBsen).
  • Analysis of metabolite initiation and maintenance over a 20-day study period.
  • Targeted analysis of citrate in two cell lines to assess its dynamic nature and relationship with p16INK4A.

Main Results:

  • The ESM of IrrDSBsen fibroblasts showed progressive alterations over 20 days, unlike transcriptional profiles.
  • Several new ESM metabolites associated with chronological aging were identified.
  • Citrate levels dynamically changed in senescent cells, independent of the senescence effector p16INK4A.

Conclusions:

  • The extracellular senescence metabolome (ESM) provides dynamic metabolic signatures of aging and cellular senescence.
  • Identified ESM metabolites can serve as potential non-invasive biomarkers for aging and senescence.
  • Understanding these metabolic signatures aids in the study of aging, senescence, and DNA damage.

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