Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner.
Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner.
复制标题
中性粒细胞以ROS依赖性方式诱导旁分泌端粒功能障碍和衰老。
DOI：
10.15252/embj.2020106048
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发表时间：
2021-05-03
期刊：
影响因子：
--
通讯作者：
Passos JF
中科院分区：
文献类型：
--
作者：
Lagnado A;Leslie J;Ruchaud-Sparagano MH;Victorelli S;Hirsova P;Ogrodnik M;Collins AL;Vizioli MG;Habiballa L;Saretzki G;Evans SA;Salmonowicz H;Hruby A;Geh D;Pavelko KD;Dolan D;Reeves HL;Grellscheid S;Wilson CH;Pandanaboyana S;Doolittle M;von Zglinicki T;Oakley F;Gallage S;Wilson CL;Birch J;Carroll B;Chapman J;Heikenwalder M;Neretti N;Khosla S;Masuda CA;Tchkonia T;Kirkland JL;Jurk D;Mann DA;Passos JF
细胞衰老的特征在于不可逆的细胞周期停滞以及促炎表型，被认为有助于衰老和年龄相关疾病。中性粒细胞在炎症反应中起着重要作用;然而，在某些情况下，它们的丰度与许多年龄相关的疾病有关，包括肝病。中性粒细胞和细胞衰老之间的关系还不清楚。在这里，我们表明非免疫细胞中的端粒对邻近中性粒细胞引起的氧化损伤非常敏感。中性粒细胞以ROS依赖性方式在体外和离体引起端粒功能障碍。在急性肝损伤的小鼠模型中，中性粒细胞的耗竭减少端粒功能障碍和衰老。最后，我们表明，衰老细胞介导的招聘中性粒细胞的老年肝脏，并提出这可能是一种机制，衰老蔓延到周围的细胞。我们的研究结果表明，对抗中性粒细胞诱导的衰老的干预措施可能对衰老和年龄相关疾病有益。炎性中性粒细胞引起的氧化损伤导致邻近细胞衰老和肝损伤。
Cellular senescence is characterized by an irreversible cell cycle arrest as well as a pro‐inflammatory phenotype, thought to contribute to aging and age‐related diseases. Neutrophils have essential roles in inflammatory responses; however, in certain contexts their abundance is associated with a number of age‐related diseases, including liver disease. The relationship between neutrophils and cellular senescence is not well understood. Here, we show that telomeres in non‐immune cells are highly susceptible to oxidative damage caused by neighboring neutrophils. Neutrophils cause telomere dysfunction both in vitro and ex vivo in a ROS‐dependent manner. In a mouse model of acute liver injury, depletion of neutrophils reduces telomere dysfunction and senescence. Finally, we show that senescent cells mediate the recruitment of neutrophils to the aged liver and propose that this may be a mechanism by which senescence spreads to surrounding cells. Our results suggest that interventions that counteract neutrophil‐induced senescence may be beneficial during aging and age‐related disease. Oxidative damage caused by inflammatory neutrophils contributes to neighbouring cell senescence and liver injury.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
82.9
作者：
Farr JN;Xu M;Weivoda MM;Monroe DG;Fraser DG;Onken JL;Negley BA;Sfeir JG;Ogrodnik MB;Hachfeld CM;LeBrasseur NK;Drake MT;Pignolo RJ;Pirtskhalava T;Tchkonia T;Oursler MJ;Kirkland JL;Khosla S
通讯作者：
Khosla S
影响因子：
64.8
作者：
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通讯作者：
van Deursen JM
DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J