What are the biomarkers of senescent cells?

From the Guidelines

Biomarkers of senescent cells include p16, p21, senescence-associated beta-galactosidase, and senescence-associated secretory phenotype (SASP) factors, as well as markers of DNA damage such as phosphorylated H2A histone family member X (γ-H2A.X) and p53-binding protein 1 (53BP1) 1. These biomarkers are used to assess cellular senescence, a stress response mechanism characterized by replication arrest and complex changes in morphology, chromatin organization, secretome, and expression of typical protein biomarkers 1. Some key points to consider when evaluating biomarkers of senescent cells include:

• The presence of unresolved DNA damage, mainly in the form of double-strand breaks (DSBs), which leads to persistent activation of the DNA damage response (DDR) 1
• The use of auxiliary markers of cellular senescence, including DNA damage, LMNB1, ALISE, oxidative damage, SASP, and SA-b-gal 1
• The importance of verifying the reduction of senescent cells and the consequences of this reduction on mouse pathology or physiology 1
• The challenges of collecting and preserving human tissues, and the need to develop senescence biomarkers compatible with minimally invasive methodologies, such as blood or urine samples 1 It is also important to note that none of the characteristic biomarkers described above are specific to senescence, and p16Ink4a is not always present 1. Therefore, a combination of biomarkers and a thorough understanding of the underlying biology are necessary to accurately assess cellular senescence. In clinical practice, the use of these biomarkers can help to identify individuals at risk of age-related diseases and to develop interventions to slow aging and improve healthspan. For example, a recent study demonstrated that the number of cells expressing p16 Ink4a in biopsy specimens of intramuscular fat was independently correlated with lower muscle strength and worse walking performance 1. Overall, the use of biomarkers of senescent cells has the potential to revolutionize our understanding of aging and age-related diseases, and to improve human healthspan.

From the Research

Biomarkers of Senescent Cells

• The senescence-associated secretory phenotype (SASP) has been identified as a driver of age-related conditions, and several proteins have been found to be elevated in all SASPs, including:
  • Growth/differentiation factor 15 (GDF15) 2
  • Stanniocalcin 1 (STC1) 2
  • Serine protease inhibitors (SERPINs) 2
• Other biomarkers of cellular senescence that have been associated with an increased risk of death in older adults include:
  • RAGE 3
  • VEGFA 3
  • PARC 3
  • MMP2 3
• Telomere length has also been recognized as a biomarker of aging, although its usefulness as a clinically important risk marker for age-related pathologies and mortality is limited 4, 5
• A combination of biomarkers, including those associated with the SASP and telomere length, may provide a more accurate prediction of health outcomes in older adults 3, 6