SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis
Yuichiro Ogata, Takaaki Yamada, Seiji Hasegawa, Ayumi Sanada, Yohei Iwata, Masaru Arima, Satoru Nakata, Kazumitsu Sugiura, Hirohiko Akamatsu
Applied Cell and Regenerative Medicine
Recently, increasing attention has been paid to senescence-associated secretory phenotype (SASP), a phenomenon that senescent cells secrete molecules such as inflammatory cytokines and matrix metalloproteinases (MMPs), due to its noxious effects on the surrounding tissue. Senescent cells in the blood and liver are known to be properly depleted by macrophages. In the dermis, accumulation of senescent cells has been reported and is thought to be involved with skin ageing. In this study, to elucidate the clearance mechanism of senescent cells in the dermis, we focused on macrophage functions. Our co-culture experiments of senescent fibroblasts and macrophages revealed a two-step clearance mechanism: first, TNF-α secreted from macrophages induces apoptosis in senescent fibroblasts, and then, dead cells are phagocytosed by macrophages. Furthermore, it was suggested that SASP factors suppress both of the two steps of the senescent cell clearance by macrophages. From these findings, normally senescent cells in the dermis are thought to be removed by macrophages, but when senescent cells are excessively accumulated owing to oxidative stress, ultraviolet (UV) ray or other reasons, SASP was suggested to suppress the macrophage-dependent clearance functions and thereby cause further accumulation of senescent cells.
Experimental dermatology
https://doi.org/10.1111/exd.14205
Published - 01-2021
10.1111/exd.14205
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Macrophages Chemical Compounds
Fibroblasts Chemical Compounds
Cellular Senescence Medicine & Life Sciences
Dermis Medicine & Life Sciences
Cells Chemical Compounds
Oxidative stress Chemical Compounds
Skin Aging Medicine & Life Sciences
Cytophagocytosis Medicine & Life Sciences
Ogata, Y., Yamada, T., Hasegawa, S., Sanada, A., Iwata, Y., Arima, M., Nakata, S., Sugiura, K., & Akamatsu, H. (2021). SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis. Experimental dermatology, 30(1), 84-91. https://doi.org/10.1111/exd.14205
Ogata, Yuichiro ; Yamada, Takaaki ; Hasegawa, Seiji ; Sanada, Ayumi ; Iwata, Yohei ; Arima, Masaru ; Nakata, Satoru ; Sugiura, Kazumitsu ; Akamatsu, Hirohiko. / SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis. In: Experimental dermatology. 2021 ; Vol. 30, No. 1. pp. 84-91.
@article{d365c90ffa964d23b7af14f8181fbcfd,
title = "SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis",
abstract = "Recently, increasing attention has been paid to senescence-associated secretory phenotype (SASP), a phenomenon that senescent cells secrete molecules such as inflammatory cytokines and matrix metalloproteinases (MMPs), due to its noxious effects on the surrounding tissue. Senescent cells in the blood and liver are known to be properly depleted by macrophages. In the dermis, accumulation of senescent cells has been reported and is thought to be involved with skin ageing. In this study, to elucidate the clearance mechanism of senescent cells in the dermis, we focused on macrophage functions. Our co-culture experiments of senescent fibroblasts and macrophages revealed a two-step clearance mechanism: first, TNF-α secreted from macrophages induces apoptosis in senescent fibroblasts, and then, dead cells are phagocytosed by macrophages. Furthermore, it was suggested that SASP factors suppress both of the two steps of the senescent cell clearance by macrophages. From these findings, normally senescent cells in the dermis are thought to be removed by macrophages, but when senescent cells are excessively accumulated owing to oxidative stress, ultraviolet (UV) ray or other reasons, SASP was suggested to suppress the macrophage-dependent clearance functions and thereby cause further accumulation of senescent cells.",
author = "Yuichiro Ogata and Takaaki Yamada and Seiji Hasegawa and Ayumi Sanada and Yohei Iwata and Masaru Arima and Satoru Nakata and Kazumitsu Sugiura and Hirohiko Akamatsu",
note = "Funding Information: We are grateful to N. Goshima (Cellisis Co., Ltd., Aichi, Japan) for her support in preparing the manuscript.",
doi = "10.1111/exd.14205",
journal = "Experimental Dermatology",
Ogata, Y, Yamada, T, Hasegawa, S, Sanada, A, Iwata, Y, Arima, M, Nakata, S, Sugiura, K & Akamatsu, H 2021, 'SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis', Experimental dermatology, vol. 30, no. 1, pp. 84-91. https://doi.org/10.1111/exd.14205
SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis. / Ogata, Yuichiro; Yamada, Takaaki; Hasegawa, Seiji; Sanada, Ayumi; Iwata, Yohei; Arima, Masaru; Nakata, Satoru; Sugiura, Kazumitsu; Akamatsu, Hirohiko.
In: Experimental dermatology, Vol. 30, No. 1, 01.2021, p. 84-91.
T1 - SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis
AU - Ogata, Yuichiro
AU - Yamada, Takaaki
AU - Hasegawa, Seiji
AU - Sanada, Ayumi
AU - Iwata, Yohei
AU - Arima, Masaru
AU - Nakata, Satoru
AU - Sugiura, Kazumitsu
AU - Akamatsu, Hirohiko
N1 - Funding Information: We are grateful to N. Goshima (Cellisis Co., Ltd., Aichi, Japan) for her support in preparing the manuscript.
N2 - Recently, increasing attention has been paid to senescence-associated secretory phenotype (SASP), a phenomenon that senescent cells secrete molecules such as inflammatory cytokines and matrix metalloproteinases (MMPs), due to its noxious effects on the surrounding tissue. Senescent cells in the blood and liver are known to be properly depleted by macrophages. In the dermis, accumulation of senescent cells has been reported and is thought to be involved with skin ageing. In this study, to elucidate the clearance mechanism of senescent cells in the dermis, we focused on macrophage functions. Our co-culture experiments of senescent fibroblasts and macrophages revealed a two-step clearance mechanism: first, TNF-α secreted from macrophages induces apoptosis in senescent fibroblasts, and then, dead cells are phagocytosed by macrophages. Furthermore, it was suggested that SASP factors suppress both of the two steps of the senescent cell clearance by macrophages. From these findings, normally senescent cells in the dermis are thought to be removed by macrophages, but when senescent cells are excessively accumulated owing to oxidative stress, ultraviolet (UV) ray or other reasons, SASP was suggested to suppress the macrophage-dependent clearance functions and thereby cause further accumulation of senescent cells.
AB - Recently, increasing attention has been paid to senescence-associated secretory phenotype (SASP), a phenomenon that senescent cells secrete molecules such as inflammatory cytokines and matrix metalloproteinases (MMPs), due to its noxious effects on the surrounding tissue. Senescent cells in the blood and liver are known to be properly depleted by macrophages. In the dermis, accumulation of senescent cells has been reported and is thought to be involved with skin ageing. In this study, to elucidate the clearance mechanism of senescent cells in the dermis, we focused on macrophage functions. Our co-culture experiments of senescent fibroblasts and macrophages revealed a two-step clearance mechanism: first, TNF-α secreted from macrophages induces apoptosis in senescent fibroblasts, and then, dead cells are phagocytosed by macrophages. Furthermore, it was suggested that SASP factors suppress both of the two steps of the senescent cell clearance by macrophages. From these findings, normally senescent cells in the dermis are thought to be removed by macrophages, but when senescent cells are excessively accumulated owing to oxidative stress, ultraviolet (UV) ray or other reasons, SASP was suggested to suppress the macrophage-dependent clearance functions and thereby cause further accumulation of senescent cells.
U2 - 10.1111/exd.14205
DO - 10.1111/exd.14205
JO - Experimental Dermatology
JF - Experimental Dermatology
Ogata Y, Yamada T, Hasegawa S, Sanada A, Iwata Y, Arima M et al. SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis. Experimental dermatology. 2021 Jan;30(1):84-91. https://doi.org/10.1111/exd.14205
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