Similarities and interplay between senescent cells and macrophages

Abstract

Senescence is a cellular program that prevents the replication of old, damaged, or cancerous cells. Senescent cells become growth arrested and undergo changes in their morphology, chromatin organization, and metabolism, and produce a bioactive secretome. This secretome, the senescence-associated secretory phenotype (SASP), mediates many of the pathophysiological effects associated with senescent cells, for example, recruiting and activating immune cells such as macrophages. The relation between senescent cells and macrophages is intriguing: senescent cells recruit macrophages, can induce them to undergo senescence, or can influence their polarization. Senescent cells and macrophages share multiple phenotypic characteristics; both have a high secretory status, increased lysosome numbers, or the ability to activate the inflammasome. Senescent cells accumulate during aging and disease, and killing them results in widespread benefits. Here we discuss similarities between senescent cells and macrophages and interpret the latest developments in macrophage biology to understand the molecular mechanisms of cellular senescence. We describe evidence and effects of senescence in macrophages and speculate on the ontogeny of the senescent-like state in macrophages. Finally, we examine the macrophage–senescent cell interplay and its impact on macrophage effector functions during inflammatory conditions and in the tumor microenvironment.

Pancreatic Cancer and Cellular Senescence: Tumor Microenvironment under the Spotlight

“…Another cell type involved in immune surveillance is macrophages [ 178 ]. Macrophages interact with senescent cells, and this interaction is indispensable for major pathophysiological processes [ 187 ]. However, the relation between senescent cells and macrophages is controversial; if on one hand, SASP can lead to senescence surveillance through the recruitment of immune cells [ 187 ], on the other, senescent cells recruit macrophages, can induce them to undergo senescence, or can influence their polarization.…”

“…Macrophages interact with senescent cells, and this interaction is indispensable for major pathophysiological processes [ 187 ]. However, the relation between senescent cells and macrophages is controversial; if on one hand, SASP can lead to senescence surveillance through the recruitment of immune cells [ 187 ], on the other, senescent cells recruit macrophages, can induce them to undergo senescence, or can influence their polarization. A recent study by Ogata et al has reported that senescent cells in the dermis are commonly removed by macrophages in a skin ageing model; however, when those cells accumulate over a certain level (e.g., following oxidative stress, UV exposure, or other stresses), the SASP suppresses the macrophage-related immune clearance of such cells [ 188 ].…”

Identification of distinct and age‐dependent p16High microglia subtypes

“…Virtually, all cells can up‐regulate p16 levels, but this induction is not always reflected by a fully senescent state. For example, p16 expression is significantly increased in aged macrophages (Hall et al, 2016 ), but p16 overexpression can also be observed in young macrophages responding to physiological stimuli (Hall et al,l., 2017 ), (Behmoaras & Gil, 2021 ).…”

Senescent Thyrocytes, Similarly to Thyroid Tumor Cells, Elicit M2-like Macrophage Polarization In Vivo

“…Xu M. and collaborators demonstrated that senescent fibroblasts transplantation in knee joint region of mice promotes an osteoarthritis-like condition, characterized by inflammation and immune cells infiltration; interestingly, transplanted senescent cells are able to recruit macrophages by the secretion of the macrophage chemoattractant MCP-1 [28]. Moreover, it has been reported that senescent cells can affect macrophages polarization [29]. Our study suggests that senescent thyrocytes (OIS) present in PTMC may be capable to establish a pro-tumoral microenvironment by triggering M2-like macrophage polarization; this could potentially represent one of the mechanisms leading to the eventual progression and poor outcome of PTMC in a subset of patients.…”