细胞衰老：透视矛盾。
Cellular senescence: putting the paradoxes in perspective.
机构信息
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA.
出版信息
Curr Opin Genet Dev. 2011 Feb;21(1):107-12. doi: 10.1016/j.gde.2010.10.005. Epub 2010 Nov 17.
Abstract
Cellular senescence arrests the proliferation of potential cancer cells, and so is a potent tumor suppressive mechanism, akin to apoptosis. Or is it? Why did cells evolve an anti-cancer mechanism that arrests, rather than kills, would-be tumor cells? Recent discoveries that senescent cells secrete growth factors, proteases and cytokines provide a shifting view--from senescence as a cell autonomous suppressor of tumorigenesis to senescence as a means to mobilize the systemic and local tissue milieu for repair. In some instances, this mobilization benefits the organism, but in others it can be detrimental. These discoveries provide potential mechanisms by which cellular senescence might contribute to the diverse, and seemingly incongruent, processes of tumor suppression, tumor promotion, tissue repair, and aging.
摘要
细胞衰老可以阻止潜在癌细胞的增殖，因此是一种强大的肿瘤抑制机制，类似于细胞凋亡。真的是这样吗？为什么细胞会进化出一种阻止而非杀死潜在肿瘤细胞的抗癌机制呢？最近的发现表明，衰老细胞会分泌生长因子、蛋白酶和细胞因子，这为我们提供了一个新的视角——从衰老作为细胞自主抑制肿瘤发生的机制转变为衰老作为动员全身和局部组织微环境进行修复的手段。在某些情况下，这种动员对生物体有益，但在其他情况下则可能有害。这些发现为细胞衰老如何有助于肿瘤抑制、肿瘤促进、组织修复和衰老等不同且看似不一致的过程提供了潜在的机制。
相似文献
1
Cellular senescence: putting the paradoxes in perspective.细胞衰老：透视矛盾。
Curr Opin Genet Dev. 2011 Feb;21(1):107-12. doi: 10.1016/j.gde.2010.10.005. Epub 2010 Nov 17.
2
To clear, or not to clear (senescent cells)? That is the question.清除，还是不清除（衰老细胞）？这就是问题所在。
Bioessays. 2016 Jul;38 Suppl 1:S56-64. doi: 10.1002/bies.201670910.
3
The senescence-associated secretory phenotype: the dark side of tumor suppression.衰老相关的分泌表型：肿瘤抑制的阴暗面。
Annu Rev Pathol. 2010;5:99-118. doi: 10.1146/annurev-pathol-121808-102144.
4
Premature aging/senescence in cancer cells facing therapy: good or bad?癌细胞在面对治疗时的早衰/衰老：是好是坏？
Biogerontology. 2016 Feb;17(1):71-87. doi: 10.1007/s10522-015-9593-9. Epub 2015 Sep 2.
5
Caveolin-1, a master regulator of cellular senescence.窖蛋白-1，细胞衰老的主要调节因子。
Cancer Metastasis Rev. 2020 Jun;39(2):397-414. doi: 10.1007/s10555-020-09875-w.
6
Four faces of cellular senescence.细胞衰老的四个方面。
J Cell Biol. 2011 Feb 21;192(4):547-56. doi: 10.1083/jcb.201009094. Epub 2011 Feb 14.
7
Senescent cells and their secretory phenotype as targets for cancer therapy.衰老细胞及其分泌表型作为癌症治疗的靶点。
Interdiscip Top Gerontol. 2013;38:17-27. doi: 10.1159/000343572. Epub 2013 Jan 17.
8
Targeting cellular senescence: A promising approach in respiratory diseases.靶向细胞衰老：呼吸疾病治疗的新策略。
Geriatr Gerontol Int. 2024 Mar;24 Suppl 1:60-66. doi: 10.1111/ggi.14653. Epub 2023 Aug 21.
9
Cellular senescence in the tumor with a bone niche microenvironment: friend or foe?具有骨龛微环境的肿瘤中的细胞衰老：朋友还是敌人？
Clin Exp Med. 2025 Jan 23;25(1):44. doi: 10.1007/s10238-025-01564-8.
10
Senescent cells as a source of inflammatory factors for tumor progression.衰老细胞作为肿瘤进展炎症因子的来源。
Cancer Metastasis Rev. 2010 Jun;29(2):273-83. doi: 10.1007/s10555-010-9220-9.
引用本文的文献
1
Adipose tissue aging as a risk factor for metabolic organ abnormalities: mechanistic insights and the role of exercise interventions.脂肪组织衰老作为代谢器官异常的一个风险因素：机制见解及运动干预的作用
Lipids Health Dis. 2025 Sep 2;24(1):274. doi: 10.1186/s12944-025-02695-3.
2
An effective system for senescence modulating drug development using quantitative high-content analysis and high-throughput screening.一种利用定量高内涵分析和高通量筛选进行衰老调节药物开发的有效系统。
Commun Biol. 2025 Aug 30;8(1):1316. doi: 10.1038/s42003-025-08758-6.
3
WSTF nuclear autophagy regulates chronic but not acute inflammation.WSTF核自噬调节慢性炎症而非急性炎症。
Nature. 2025 Jul 2. doi: 10.1038/s41586-025-09234-1.
4
Advances in Molecular Research of Tracheobronchial Tree Aging: A Systematic Review.气管支气管树老化的分子研究进展：一项系统综述
Int J Mol Sci. 2025 May 27;26(11):5128. doi: 10.3390/ijms26115128.
5
A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.癌症与衰老中端粒损耗的综述：当前的分子见解及未来的治疗方法
Cancers (Basel). 2025 Jan 14;17(2):257. doi: 10.3390/cancers17020257.
6
ATRX loss inhibits DDR to strengthen radio-sensitization in p53-deficent HCT116 cells.ATRX缺失抑制DNA损伤修复（DDR）以增强p53缺陷型HCT116细胞的放射敏感性。
Sci Rep. 2025 Jan 4;15(1):793. doi: 10.1038/s41598-024-85085-6.
7
Decreased telomerase activity and shortened telomere length in infants whose mothers have gestational diabetes mellitus and increased severity of telomere shortening in male infants.母亲患有妊娠期糖尿病的婴儿端粒酶活性降低、端粒长度缩短，且男婴端粒缩短的严重程度增加。
Front Endocrinol (Lausanne). 2024 Dec 16;15:1490336. doi: 10.3389/fendo.2024.1490336. eCollection 2024.
8
Telomere length as a biomarker for cerebrovascular diseases: current evidence.端粒长度作为脑血管疾病的生物标志物：当前证据。
Mol Biol Rep. 2024 Nov 13;51(1):1150. doi: 10.1007/s11033-024-10077-8.
9
Piwi mutant germ cells transmit a form of heritable stress that promotes longevity.Piwi突变生殖细胞传递一种可促进长寿的遗传性应激形式。
Aging Cell. 2025 Jan;24(1):e14350. doi: 10.1111/acel.14350. Epub 2024 Nov 9.
10
In Vitro Treatment with Metformin Significantly Reduces Senescent B Cells Present in the Adipose Tissue of People with Obesity.二甲双胍的体外治疗显著减少肥胖人群脂肪组织中存在的衰老B细胞。
J Nutr. 2025 Feb;155(2):445-452. doi: 10.1016/j.tjnut.2024.10.013. Epub 2024 Oct 9.
本文引用的文献
1
DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion.DNA-SCARS：维持损伤诱导衰老生长停滞和炎性细胞因子分泌的独特核结构。
J Cell Sci. 2011 Jan 1;124(Pt 1):68-81. doi: 10.1242/jcs.071340. Epub 2010 Nov 30.
2
The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing.基质细胞蛋白 CCN1 诱导成纤维细胞衰老并限制皮肤伤口愈合中的纤维化。
Nat Cell Biol. 2010 Jul;12(7):676-85. doi: 10.1038/ncb2070. Epub 2010 Jun 6.
3
Inflammatory networks during cellular senescence: causes and consequences.细胞衰老过程中的炎症网络：原因与后果。
Trends Mol Med. 2010 May;16(5):238-46. doi: 10.1016/j.molmed.2010.03.003. Epub 2010 May 3.
4
Immunity, inflammation, and cancer.免疫、炎症与癌症。
Cell. 2010 Mar 19;140(6):883-99. doi: 10.1016/j.cell.2010.01.025.
5
A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.在依赖生理氧的小鼠细胞中，存在一种类似人类衰老相关分泌表型的表型。
PLoS One. 2010 Feb 12;5(2):e9188. doi: 10.1371/journal.pone.0009188.
6
The senescence-associated secretory phenotype: the dark side of tumor suppression.衰老相关的分泌表型：肿瘤抑制的阴暗面。
Annu Rev Pathol. 2010;5:99-118. doi: 10.1146/annurev-pathol-121808-102144.
7
Senescence in tumours: evidence from mice and humans.肿瘤衰老：来自小鼠和人类的证据。
Nat Rev Cancer. 2010 Jan;10(1):51-7. doi: 10.1038/nrc2772.
8
DNA damage response and cellular senescence in tissues of aging mice.衰老小鼠组织中的DNA损伤反应与细胞衰老
Aging Cell. 2009 Jun;8(3):311-23. doi: 10.1111/j.1474-9726.2009.00481.x. Epub 2009 Apr 9.
9
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion.持续性DNA损伤信号传导触发衰老相关炎性细胞因子的分泌。
Nat Cell Biol. 2009 Aug;11(8):973-9. doi: 10.1038/ncb1909. Epub 2009 Jul 13.
10
Caveolin-1 regulates the antagonistic pleiotropic properties of cellular senescence through a novel Mdm2/p53-mediated pathway.小窝蛋白-1通过一条新的Mdm2/p53介导的途径调节细胞衰老的拮抗性多效性特性。
Cancer Res. 2009 Apr 1;69(7):2878-86. doi: 10.1158/0008-5472.CAN-08-2857. Epub 2009 Mar 24.
Zotero 插件