Research Paper Volume 8, Issue 7 pp 1294—1315

Figure 5. Schematic of hypothetical model of in vivo accumulation of p16(Ink4a)/β-gal^pH6-positive cells in naturally aged organisms. In young mammals (top panel), the secretion of SASP by p16(Ink4a)/β-gal^pH6-positive SCs facilitates the attraction of innate immune components necessary for efficient targeting and destruction of SCs. SC secretions activate recruited macrophages, inducing a p16(Ink4a)/β-gal^pH6-positive phenotype in them. After the successful eradication of SCs, inflammatory factors subside and tissue homeostasis resumes. This resolution results in the loss of p16(Ink4a)/β-gal^pH6-positive cells from the tissue, as macrophages with this phenotype are cleared or discharge their activated state. However, in old animals (bottom panel), impairments in innate immunity result in the inability to efficiently recognize or destroy SCs. This results in establishment of chronic, inflammation induced by products of secretion of SCs and SC-associated macrophages (SAM). Accumulation of SAMs can be a manifestation of unresolved innate immune response leading to chronic sterile systemic inflammation typical for aged organisms.