切换至 "中华医学电子期刊资源库"

中华老年病研究电子杂志 ›› 2022, Vol. 09 ›› Issue (02) : 1 -8. doi: 10.3877/cma.j.issn.2095-8757.2022.02.001

衰老和老化

衰老机制及抗衰老研究新进展
张婧1, 毛根祥1,()   
  1. 1. 310013 杭州,浙江省老年医学研究所 浙江省老年医学重点实验室
  • 收稿日期:2022-04-11 出版日期:2022-05-28
  • 通信作者: 毛根祥
  • 基金资助:
    国家自然科学基金项目(81771520、81701393); 浙江省自然科学基金项目(LY21H250001); 浙江省卫生健康科技计划项目(2021KY014)

Advances in the study of aging mechanism and anti-aging research

Jing Zhang1, Genxiang Mao1()   

  1. 1. Zhejiang Provincial Key Lab of Geriatrics, Geriatrics Institute of Zhejiang Province, Hangzhou 310013, China
  • Received:2022-04-11 Published:2022-05-28
  • Corresponding author: Genxiang Mao
引用本文:

张婧, 毛根祥. 衰老机制及抗衰老研究新进展[J/OL]. 中华老年病研究电子杂志, 2022, 09(02): 1-8.

Jing Zhang, Genxiang Mao. Advances in the study of aging mechanism and anti-aging research[J/OL]. Chinese Journal of Geriatrics Research(Electronic Edition), 2022, 09(02): 1-8.

衰老是指随着年龄的增长,机体生理功能发生逐渐衰退的过程。细胞衰老在多种年龄相关疾病中起重要作用。在不同生物体中发现的衰老特征包括基因组不稳定性、端粒磨损、表观遗传改变、蛋白质稳态丧失、营养感应失调、线粒体功能障碍、细胞衰老、干细胞衰竭和细胞间通讯改变。本文重点综述了近年来衰老相关研究的新进展,包括与衰老相关的分子机制、衰老研究领域的新技术,以及抗衰老研究的新成果,并对衰老机制和抗衰老研究的未来发展进行了展望。

Aging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. Cellular senescence plays an important role in a variety of age-related diseases. The hallmarks of aging identified in different organisms, include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. This paper reviews the new research progress on aging in recent 3 years, which includes senescence related signaling pathways and mechanisms, new technologies in the field of aging research, and new achievements in anti-aging research, and finally prospects the future development of aging mechanism and anti-aging research.

[1]
Kennedy BK, Berger SL, Brunet A, et al. Geroscience: Linking aging to chronic disease[J]. Cell, 2014, 159(4):709-713.
[2]
Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging[J]. Cell, 2013, 153(6):1194-1217.
[3]
Forman DE, Maurer MS, Boyd C, et al. Multimorbidity in older adults with cardiovascular disease[J]. J Am Coll Cardiol, 2018, 71(19):2149-2161.
[4]
Barnett K, Mercer SW, Norbury M, et al. Epidemiology of multimorbidity and implications for health care, research, and medical education: A cross-sectional study[J]. Lancet, 2012, 380(9836):37-43.
[5]
Kirkland JL, Tchkonia T. Senolytic drugs: From discovery to translation[J]. J Intern Med, 2020, 288(5):518-536.
[6]
Zhang P, Kishimoto Y, Grammatikakis I, et al. Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model[J]. Nat Neurosci, 2019, 22(5):719-728.
[7]
Xu M, Bradley EW, Weivoda MM, et al. Transplanted senescent cells induce an osteoarthritis-like condition in mice[J]. J Gerontol A Biol Sci Med Sci, 2017, 72(6):780-785.
[8]
Palmer AK, Gustafson B, Kirkland JL, et al. Cellular senescence: At the nexus between ageing and diabetes[J]. Diabetologia, 2019, 62(10):1835-1841.
[9]
Boulestreau J, Maumus M, Jorgensen C, et al. Extracellular vesicles from mesenchymal stromal cells: Therapeutic perspectives for targeting senescence in osteoarthritis[J]. Adv Drug Deliv Rev, 2021, 175:113836.
[10]
Covarrubias AJ, Perrone R, Grozio A, et al. NAD(+) metabolism and its roles in cellular processes during ageing[J]. Nat Rev Mol Cell Biol, 2021, 22(2):119-141.
[11]
Gan L, Liu D, Liu J, et al. CD38 deficiency alleviates AngⅡ-induced vascular remodeling by inhibiting small extracellular vesicle-mediated vascular smooth muscle cell senescence in mice[J]. Signal Transduct Target Ther, 2021, 6(1):223.
[12]
Diehl FF, Lewis CA, Fiske BP, et al. Cellular redox state constrains serine synthesis and nucleotide production to impact cell proliferation[J]. Nat Metab, 2019, 1(9):861-867.
[13]
Yang L, Garcia Canaveras JC, Chen Z, et al. Serine catabolism feeds nadh when respiration is impaired[J]. Cell Metab, 2020, 31(4):809-821.e806.
[14]
Liu S, Fu S, Wang G, et al. Glycerol-3-phosphate biosynthesis regenerates cytosolic NAD(+) to alleviate mitochondrial disease[J]. Cell Metab, 2021, 33(10):1974-1987.e1979.
[15]
Hou Y, Wei Y, Lautrup S, et al. NAD(+) supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer's disease via cGAS-STING[J/OL]. Proc Natl Acad Sci U S A, 2021, 118(37):e2011226118.
[16]
Zeidan RS, Han SM, Leeuwenburgh C, et al. Iron homeostasis and organismal aging[J]. Ageing Res Rev, 2021, 72:101510.
[17]
Ayton S, Portbury S, Kalinowski P, et al. Regional brain iron associated with deterioration in Alzheimer's disease: A large cohort study and theoretical significance[J]. Alzheimers Dement, 2021, 17(7):1244-1256.
[18]
Milanese C, Gabriels S, Barnhoorn S, et al. Gender biased neuroprotective effect of Transferrin Receptor 2 deletion in multiple models of Parkinson's disease[J]. Cell Death Differ, 2021, 28(5):1720-1732.
[19]
Kitazoe Y, Kishino H, Tanisawa K, et al. Renormalized basal metabolic rate describes the human aging process and longevity[J/OL]. Aging Cell, 2019, 18(4):e12968.
[20]
Mazhar M, Din AU, Ali H, et al. Implication of ferroptosis in aging[J]. Cell Death Discov, 2021, 7(1):149.
[21]
Timmers P, Wilson JF, Joshi PK, et al. Multivariate genomic scan implicates novel loci and haem metabolism in human ageing[J]. Nat Commun, 2020, 11(1):3570.
[22]
Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5):1060-1072.
[23]
Lee J, You JH, Shin D, et al. Inhibition of glutaredoxin 5 predisposes cisplatin-resistant head and neck cancer cells to ferroptosis[J]. Theranostics, 2020, 10(17):7775-7786.
[24]
Kajarabille N, Latunde-Dada GO. Programmed cell-death by ferroptosis: Antioxidants as mitigators[J]. Int J Mol Sci, 2019, 20(19):4968.
[25]
Wei Z, Hao C, Huangfu J, et al. Aging lens epithelium is susceptible to ferroptosis[J]. Free Radic Biol Med, 2021, 167:94-108.
[26]
Sfera A, Bullock K, Price A, et al. Ferrosenescence: The iron age of neurodegeneration[J]? Mech Ageing Dev, 2018, 174:63-75.
[27]
Zhu HY, He QJ, Yang B, et al. Beyond iron deposition: Making sense of the latest evidence on ferroptosis in Parkinson's disease[J]. Acta Pharmacol Sin, 2021, 42(9):1379-1381.
[28]
Lane DJR, Metselaar B, Greenough M, et al. Ferroptosis and NRF2: An emerging battlefield in the neurodegeneration of Alzheimer's disease[J]. Essays Biochem, 2021, 65(7):925-940.
[29]
David S, Jhelum P, Ryan F, et al. Dysregulation of iron homeostasis in the central nervous system and the role of ferroptosis in neurodegenerative disorders[J]. Antioxid Redox Signal, 2022, doi: 10.1089/ars.2021.0218.
[30]
Martínez I, García-Carpizo V, Guijarro T, et al. Induction of DNA double-strand breaks and cellular senescence by human respiratory syncytial virus[J]. Virulence, 2016, 7(4):427-442.
[31]
Chuprin A, Gal H, Biron-Shental T, et al. Cell fusion induced by ERVWE1 or measles virus causes cellular senescence[J]. Genes Dev, 2013, 27(21):2356-2366.
[32]
Kohli J, Veenstra I, Demaria M. The struggle of a good friend getting old: Cellular senescence in viral responses and therapy[J/OL]. EMBO Rep, 2021, 22(4):e52243.
[33]
Wiersinga WJ, Rhodes A, Cheng AC, et al. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A review[J]. JAMA, 2020, 324(8):782-793.
[34]
Park SC, Won SY, Kim NH, et al. Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections: A nationwide population-based study[J]. Ann Transl Med, 2021, 9(3):211.
[35]
Borczuk AC, Salvatore SP, Seshan SV, et al. COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City[J]. Mod Pathol, 2020, 33(11):2156-2168.
[36]
Wang S, Yao X, Ma S, et al. A single-cell transcriptomic landscape of the lungs of patients with COVID-19[J]. Nat Cell Biol, 2021, 23(12):1314-1328.
[37]
D'Agnillo F, Walters KA, Xiao Y, et al. Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19[J]. Sci Transl Med, 2021, 13(620):eabj7790.
[38]
Tsuji S, Minami S, Hashimoto R, et al. SARS-CoV-2 infection triggers paracrine senescence and leads to a sustained senescence-associated inflammatory response[J]. Nature Aging, 2022, 2(2):115-124.
[39]
Meyer K, Patra T, Vijayamahantesh, et al. SARS-CoV-2 spike protein induces paracrine senescence and leukocyte adhesion in endothelial cells[J/OL]. J Virol, 2021, 95(17):e0079421.
[40]
Lee S, Yu Y, Trimpert J, Benthani F, et al. Virus-induced senescence is a driver and therapeutic target in COVID-19[J]. Nature, 2021, 599(7884):283-289.
[41]
Vaz B, Vuotto C, Valvo S, et al. Intercellular telomere transfer extends T cell lifespan[J/OL]. bioRxiv, 2020, doi:10.1101/2020.10.09.331918.
[42]
Bonafè M, Sabbatinelli J, Olivieri F. Exploiting the telomere machinery to put the brakes on inflamm-aging[J]. Ageing Res Rev, 2020, 59:101027.
[43]
Storci G, Bonifazi F, Garagnani P, et al. The role of extracellular DNA in COVID-19: Clues from inflamm-aging[J]. Ageing Res Rev, 2021, 66:101234.
[44]
Chen G, Ning B, Shi T. Single-cell RNA-seq technologies and related computational data analysis[J]. Front Genet, 2019, doi: 10.3389/fgene.2019.00317.
[45]
Andrews TS, Hemberg M. Identifying cell populations with scRNASeq[J]. Mol Aspects Med, 2018, 59:114-122.
[46]
Ma S, Sun S, Li J, et al. Single-cell transcriptomic atlas of primate cardiopulmonary aging[J]. Cell Res, 2021, 31(4):415-432.
[47]
Huang Z, Chen B, Liu X, et al. Effects of sex and aging on the immune cell landscape as assessed by single-cell transcriptomic analysis[J]. Proc Natl Acad Sci U S A, 2021, 118(33).
[48]
Zou Z, Long X, Zhao Q, et al. A single-cell transcriptomic atlas of human skin aging[J]. Dev Cell, 2021, 56(3):383-397.e388.
[49]
Zhang H, Li J, Ren J, et al. Single-nucleus transcriptomic landscape of primate hippocampal aging[J]. Protein Cell, 2021, 12(9):695-716.
[50]
Zhang L, Pitcher LE, Prahalad V, et al. Targeting cellular senescence with senotherapeutics: Senolytics and senomorphics[J]. FEBS J, 2022, doi: 10.1111/febs.16350.
[51]
Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: From transcriptome to senolytic drugs[J]. Aging Cell, 2015, 14(4):644-658.
[52]
Wissler Gerdes EO, Zhu Y, Tchkonia T, et al. Discovery, development, and future application of senolytics: theories and predictions[J]. FEBS J, 2020, 287(12):2418-2427.
[53]
Saccon TD, Nagpal R, Yadav H, et al. Senolytic combination of dasatinib and quercetin alleviates intestinal senescence and inflammation and modulates the gut microbiome in aged mice[J]. J Gerontol A Biol Sci Med Sci, 2021, 76(11):1895-1905.
[54]
Bourgeois B, Madl T. Regulation of cellular senescence via the FOXO4-p53 axis[J]. FEBS Lett, 2018, 592(12):2083-2097.
[55]
Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging[J]. Cell, 2017, 169(1):132-147.e116.
[56]
Li L, Lu N, Dai Q, et al. GL-V9, a newly synthetic flavonoid derivative, induces mitochondrial-mediated apoptosis and G2/M cell cycle arrest in human hepatocellular carcinoma HepG2 cells[J]. Eur J Pharmacol, 2011, 670(1):13-21.
[57]
Zhao Y, Guo Q, Zhao K, et al. Small molecule GL-V9 protects against colitis-associated colorectal cancer by limiting NLRP3 inflammasome through autophagy[J/OL]. Oncoimmunology, 2017, 7(1):e1375640.
[58]
Zhu Y, Liu M, Yao J, et al. The synthetic flavonoid derivative GL-V9 induces apoptosis and autophagy in cutaneous squamous cell carcinoma via suppressing AKT-regulated HK2 and mTOR signals[J]. Molecules, 2020, 25(21):5033.
[59]
Yang D, Tian X, Ye Y, et al. Identification of GL-V9 as a novel senolytic agent against senescent breast cancer cells[J]. Life Sci, 2021, 272:119196.
[60]
Zhang X, Dong Y, Li WC, et al. Roxithromycin attenuates bleomycin-induced pulmonary fibrosis by targeting senescent cells[J]. Acta Pharmacol Sin, 2021, 42(12):2058-2068.
[61]
Woo J, Shin S, Cho E, et al. Senotherapeutic-like effect of silybum marianum flower extract revealed on human skin cells[J/OL]. PloS One, 2021, 16(12):e0260545.
[62]
Xu Q, Fu Q, Li Z, et al. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice[J]. Nat Metab, 2021, 3(12):1706-1726.
[63]
Selvarani R, Mohammed S, Richardson A. Effect of rapamycin on aging and age-related diseases—past and future[J]. Geroscience, 2021, 43(3):1135-1158.
[64]
Bjedov I, Rallis C. The target of rapamycin signalling pathway in ageing and lifespan regulation[J]. Genes, 2020, 11(9):1043.
[65]
Foretz M, Guigas B, Bertrand L, et al. Metformin: From mechanisms of action to therapies[J]. Cell Metab, 2014, 20(6):953-966.
[66]
Hu D, Xie F, Xiao Y, et al. Metformin: A potential candidate for targeting aging mechanisms[J]. Aging Dis, 2021, 12(2):480-493.
[67]
Chen C, Zhou M, Ge Y, et al. SIRT1 and aging related signaling pathways[J]. Mech Ageing Dev, 2020, 187:111215.
[68]
Liu J, Jiao K, Zhou Q, et al. Resveratrol alleviates 27-hydroxycholesterol-induced senescence in nerve cells and affects zebrafish locomotor behavior via activation of SIRT1-mediated STAT3 signaling[J]. Oxid Med Cell Longev, 2021, 2021:6673343.
[69]
Mao GX, Xu XG, Wang SY, et al. Salidroside delays cellular senescence by stimulating mitochondrial biogenesis partly through a miR-22/SIRT-1 pathway[J]. Oxid Med Cell Longev, 2019, 2019:5276096.
[70]
Tang Y, Hou Y, Zeng Y, et al. Salidroside attenuates CoCl(2)-simulated hypoxia injury in PC12 cells partly by mitochondrial protection[J]. Eur J Pharmacol, 2021, 912:174617.
[71]
Zhang L, Zhao J, Mu X, et al. Novel small molecule inhibition of IKK/NF-κB activation reduces markers of senescence and improves healthspan in mouse models of aging[J/OL]. Aging Cell, 2021, 20(12):e13486.
[1] 于桐, 孙姗姗, 刘扬. 乳腺导管原位癌的浸润转化机制及临床病理特征[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(05): 304-307.
[2] 李蓉. 薄型子宫内膜治疗新方法[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 591-591.
[3] 严华悦, 刘子祥, 周少波. 磷酸烯醇式丙酮酸羧激酶-1在恶性肿瘤中的研究进展[J/OL]. 中华普通外科学文献(电子版), 2024, 18(06): 452-456.
[4] 胡思平, 熊性宇, 徐航, 杨璐. 衰老相关分泌表型因子在前列腺癌发生发展中的作用机制[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(05): 425-434.
[5] 刘璐璐, 何羽. 慢性阻塞性肺病患者睡眠障碍的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 836-839.
[6] 袁园园, 岳乐淇, 张华兴, 武艳, 李全海. 间充质干细胞在呼吸系统疾病模型中肺组织分布及治疗机制的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 374-381.
[7] 王庭宇, 邵联波, 刘珊, 沈振亚. Stanford A 型主动脉夹层相关基因KIF20A 的共表达网络构建及作用靶点分析[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 303-312.
[8] 孟煜凡, 李永政, 樊知遥, 展翰翔. 瘤内微生物在胰腺癌发病和演进中的作用机制及研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(04): 577-582.
[9] 赵泽云, 李建男, 王旻. 中性粒细胞胞外诱捕网在结直肠癌中的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 524-528.
[10] 王梦琪, 刘恒昌, 陈海鹏, 刘佳. 骶神经刺激治疗排便失禁的机制研究进展[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 417-422.
[11] 陈利, 杨长青, 朱风尚. 重视炎症性肠病和代谢相关脂肪性肝病间的串话机制研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 385-389.
[12] 刘琦, 王守凯, 王帅, 苏雨晴, 马壮, 陈海军, 司丕蕾. 乳腺癌肿瘤内微生物组的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 841-845.
[13] 徐靖亭, 孔璐. PARP抑制剂治疗卵巢癌的耐药机制及应对策略[J/OL]. 中华临床医师杂志(电子版), 2024, 18(06): 584-588.
[14] 周佳佳, 俞莹, 梁舒. 视频终端视相关性干眼症的机制研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(04): 402-406.
[15] 曹亚丽, 高雨萌, 张英谦, 李博, 杜军保, 金红芳. 儿童坐位不耐受的临床进展[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(05): 510-515.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?