p16INK4a

Definition

p16INK4a is a tumour-suppressor protein encoded by the CDKN2A gene. It inhibits cyclin-dependent kinases CDK4 and CDK6, helping enforce cell-cycle arrest by maintaining retinoblastoma protein activity. In ageing biology, increased p16INK4a expression is commonly used as a marker associated with cellular senescence. [1] [2] [3]

Why It Matters in Ageing Research

p16INK4a matters because it links cell-cycle control, tumour suppression, senescence, and tissue ageing. Its expression tends to rise with age in several tissues and has been used to identify or track senescent-cell burden in experimental and translational studies. However, p16INK4a is best interpreted alongside other markers because no single marker defines all senescent cells in every tissue or context. [4] [5] [6]

Common Confusion

• p16INK4a is a senescence-associated marker, but p16INK4a expression alone does not prove that a cell is senescent.
• p16INK4a is not the same as p21; both are cell-cycle inhibitors, but they act through different pathways.
• Higher p16INK4a can reflect protective tumour-suppressor responses as well as age-related accumulation of senescent cells.

Related Reading

• Cellular Senescence
• SASP
• Senolytics
• DNA Damage Response
• p21

References

1. Serrano, M., Hannon, G. J., & Beach, D. (1993). A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. https://doi.org/10.1038/366704a0
2. Sherr, C. J., & Roberts, J. M. (1999). CDK inhibitors: positive and negative regulators of G1-phase progression. https://doi.org/10.1101/gad.13.12.1501
3. Collado, M., Blasco, M. A., & Serrano, M. (2007). Cellular Senescence in Cancer and Aging. https://doi.org/10.1016/j.cell.2007.07.003
4. Krishnamurthy, J., Torrice, C., Ramsey, M. R., et al. (2004). Ink4a/Arf expression is a biomarker of aging. https://doi.org/10.1172/JCI22475
5. Baker, D. J., Wijshake, T., Tchkonia, T., et al. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. https://doi.org/10.1038/nature10600
6. Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018). Hallmarks of Cellular Senescence. https://doi.org/10.1016/j.tcb.2018.02.001