p16(Ink4a) and senescence-associated β-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli.
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Hall BM, Balan V, Gleiberman AS, Strom E, Krasnov P, Virtuoso LP, Rydkina E, Vujcic S, Balan K, Gitlin II, Leonova KI, Consiglio CR, Gollnick SO, Chernova OB, Gudkov AV
Aging (Albany NY) 9 (8) 1867-1884 [2017-08-02; online 2017-08-05]
Constitutive p16 expression, along with senescence-associated β-galactosidase (SAβG), are commonly accepted biomarkers of senescent cells (SCs). Recent reports attributed improvement of the healthspan of aged mice following Ink4ap16-positive cell killing to the eradication of accumulated SCs. However, detection of Ink4ap16/SAβG-positive macrophages in the adipose tissue of old mice and in the peritoneal cavity of young animals following injection of alginate-encapsulated SCs has raised concerns about the exclusivity of these markers for SCs. Here we report that expression of Ink4ap16 and SAβG in macrophages is acquired as part of a physiological response to immune stimuli rather than through senescence, consistent with reports that p16Ink4aInk4a plays a role in macrophage polarization and response. Unlike SCs, p16/SAβG-positive macrophages can be induced in p53-null mice. Macrophages, but not mesenchymal SCs, lose both markers in response to M1- [LPS, IFN-α, Poly(I:C)] and increase their expression in response to M2-inducing stimuli (IL-4, IL-13). Moreover, interferon-inducing agent Poly(I:C) dramatically reduced Ink4ap16 expression Ink4ain vivo in our alginate bead model and in the adipose tissue of aged mice. These observations suggest that the antiaging effects following eradication of p16-positive cells may not be solely attributed to SCs but also to non-senescent Ink4ap16/SAβG-positive macrophages.Ink4a
PubMed 28768895
DOI 10.18632/aging.101268
Crossref 10.18632/aging.101268
pmc: PMC5611982
pii: 101268