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Aging (Albany NY). 2017 Aug 2;9(8):1867-1884. doi: 10.18632/aging.101268.

p16(Ink4a) and senescence-associated β-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli.

Author information

1
Everon Biosciences, Inc., Buffalo, NY 14203, USA.
2
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
3
Department of Tumor Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Abstract

Constitutive p16Ink4a 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 p16Ink4a-positive cell killing to the eradication of accumulated SCs. However, detection of p16Ink4a/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 p16Ink4a and SAβG in macrophages is acquired as part of a physiological response to immune stimuli rather than through senescence, consistent with reports that p16Ink4a plays a role in macrophage polarization and response. Unlike SCs, p16Ink4a/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 p16Ink4a expression in vivo in our alginate bead model and in the adipose tissue of aged mice. These observations suggest that the antiaging effects following eradication of p16Ink4a-positive cells may not be solely attributed to SCs but also to non-senescent p16Ink4a/SAβG-positive macrophages.

KEYWORDS:

aging; beta-galactosidase; macrophage; p16(Ink4a); senescent cell

PMID:
28768895
PMCID:
PMC5611982
DOI:
10.18632/aging.101268
[Indexed for MEDLINE]
Free PMC Article

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