Global changes and markers of senescent cells. During ageing, the accumulation of senescent cells is often observed. Senescent cells are characterized by permanent cell cycle arrest, increased size, elevated activity of senescence associated β galactosidase (SA-β-gal) and higher levels of cell cycle inhibitors, p16 and/or p21. Moreover, senescent cells secrete various proteins such as cytokines, growth factors and proteases. This phenomenon is generally referred as senescence associated secretory phenotype (SASP). Nuclear changes are manifested by disrupted structure of nuclear lamina (for instance, due to downregulation of Lamin B1), local condensation of chromatin in the form of senescent associated heterochromatin foci (SAHF) and by DNA-SCARS (DNA segments with chromatin alterations reinforcing senescence), which form in response to DNA damage.