New Horizons in cellular senescence for clinicians.
New Horizons in cellular senescence for clinicians.
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DOI：
10.1093/ageing/afad127
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发表时间：
2023-07-01
期刊：
影响因子：
6.7
通讯作者：
Sayer, Avan A.
中科院分区：
文献类型：
--
作者：
Witham, Miles D.;Granic, Antoneta;Miwa, Satomi;Passos, Joao F.;Richardson, Gavin D.;Sayer, Avan A.
关键词：
细胞衰老已成为支撑衰老过程的基本生物学机制，并与越来越多的与年龄有关的疾病的发病机制有关。细胞衰老是一种细胞命运，最初被定义为复制潜力的不可逆丧失，尽管现在清楚的是，它可以由多种机制诱导，而不依赖于复制和端粒磨损。驱动因素包括持续的DNA损伤反应，导致细胞功能的多种改变。衰老细胞分泌一系列介质，驱动慢性炎症，并可将其他细胞转化为衰老状态-衰老相关分泌表型。迄今为止，许多研究都是在动物模型中进行的，但现在很清楚，衰老细胞伴随着人类的衰老，它们的存在是跨系统疾病的重要驱动因素。概念验证工作表明，预防或逆转衰老可能是对抗人类衰老和与年龄有关的疾病的可行策略。可能的干预措施包括运动，营养和senolytics/senostatic药物，尽管senotherapeutics的使用有一些潜在的限制。这些干预措施通常是针对单一器官的情况进行测试，但这种方法的真实的力量是解决多种年龄相关疾病的潜力。然而，这类令人兴奋的新疗法的试金石将是它们是否能改善健康的预期寿命，而不仅仅是延长寿命。如果senotherapeutics要获得临床医生，患者和公众的信任，临床研究中测量的结果需要反映这些目标。
Cellular senescence has emerged as a fundamental biological mechanism underpinning the ageing process and has been implicated in the pathogenesis of an increasing number of age-related conditions. Cellular senescence is a cell fate originally defined as an irreversible loss of replicative potential although it is now clear that it can be induced by a variety of mechanisms independent of replication and telomere attrition. The drivers include a persistent DNA damage response causing multiple alterations in cellular function. Senescent cells secrete a range of mediators that drive chronic inflammation and can convert other cells to the senescent state—the senescence-associated secretory phenotype. Much research to date has been conducted in animal models, but it is now clear that senescent cells accompany ageing in humans and their presence is an important driver of disease across systems. Proof-of-concept work suggests that preventing or reversing senescence may be a viable strategy to counteract human ageing and age-related disease. Possible interventions include exercise, nutrition and senolytics/senostatic drugs although there are a number of potential limitations to the use of senotherapeutics. These interventions are generally tested for single-organ conditions, but the real power of this approach is the potential to tackle multiple age-related conditions. The litmus test for this exciting new class of therapies, however, will be whether they can improve healthy life expectancy rather than merely extending lifespan. The outcomes measured in clinical studies need to reflect these aims if senotherapeutics are to gain the trust of clinicians, patients and the public.
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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：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
DOI：
10.1083/jcb.201610113
发表时间：
2017-07-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carroll B;Nelson G;Rabanal-Ruiz Y;Kucheryavenko O;Dunhill-Turner NA;Chesterman CC;Zahari Q;Zhang T;Conduit SE;Mitchell CA;Maddocks ODK;Lovat P;von Zglinicki T;Korolchuk VI
通讯作者：
Korolchuk VI
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
影响因子：
7.3
作者：
Spray L;Park C;Cormack S;Mohammed A;Panahi P;Boag S;Bennaceur K;Sopova K;Richardson G;Stangl VM;Rech L;Rainer PP;Ramos GC;Hofmann U;Stellos K;Spyridopoulos I
通讯作者：
Spyridopoulos I