title: Ageing as developmental decay: insights from p16(INK4a.).
abstract: The p16(INK4a) cell cycle regulator is one of the best ageing biomarkers because it is suppressed in early embryogenesis and progressively induced during ageing. p16(INK4a) plays a crucial role in key cell fate decisions which contribute to ageing, such as cellular senescence and stem cell dynamics. Detailed examination of the pathways regulating p16(INK4a) expression has revealed an overlap with those regulating early development. We present the hypothesis that ageing might be primarily driven by gradual functional decay of developmental pathways. To support this, we summarise the role of p16(INK4a) in ageing and our current knowledge on p16(INK4a) regulation. The developmental decay hypothesis implies that the much-evidenced damage associated with all aspects of ageing might be secondary to such decay.
authors.affiliation: Cell Proliferation Group, Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
authors.forename: Nadine
authors.initials: N
authors.lastname: Martin
authors.affiliation: Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London E1 2AT, UK. Electronic address: dhbeach@btinternet.com.
authors.forename: David
authors.initials: D
authors.lastname: Beach
authors.affiliation: Cell Proliferation Group, Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London W12 0NN, UK. Electronic address: jesus.gil@csc.mrc.ac.uk.
authors.forename: Jesús
authors.initials: J
authors.lastname: Gil
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000502:physiology*; D063185:Epigenetic Repression; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D005819:Genetic Markers; D006801:Humans; D023421:Models, Animal
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers
keywords: ageing; development; p16(INK4a); senescence