Maximus Peto’s Commentary
This group reports that irreparable double-strand breaks in fibroblasts are characterized by an “extracellular senescence metabolome” that evolves, and some of these metabolites are associated with chronological aging. They also report that some of these metabolites are independent of p16INK4A.
The induction of the fibroblast extracellular senescence metabolome is a dynamic process.
Sci Rep. 2018 Aug 14;8(1):12148.
James ENL, Bennett MH, Parkinson EK
PubMed publication date (edat): 8/16/2018
Cellular senescence is often associated with irreparable DNA double strand breaks (IrrDSBs) which accumulate with chronological age (IrrDSBsen). The removal of senescent cells ameliorates several age-related diseases in mice but the translation of these findings into a clinical setting would be aided by the characterisation of non-invasive biomarkers of senescent cells. Several serum metabolites are independent indicators of chronological age and some of these accumulate outside senescent fibroblasts independently of cell cycle arrest, repairable DNA breaks and cell size (the extracellular senescence metabolome, or ESM). The post-mitotic phase of senescence is dynamic, making the detection of senescent cells in vivo difficult. An unbiased metabolomic screen of the IrrDSBsen fibroblast ESM also showed differences in the times of initiation and maintenance of different metabolites but generally the ESM altered progressively over the 20 day study period unlike the reported transcriptional profiles. This more detailed analysis of IrrDSBsen identified several new ESM metabolites that are associated with chronological ageing. Targeted analysis of citrate confirmed the dynamic nature of this metabolite in two cell lines and revealed its independence from the senescence effector p16INK4A. These data will aid our understanding of metabolic signatures of ageing and their relationship to cellular senescence and IrrDSBs.
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092376/