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]. 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]. 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] 张晓燕, 肖东琼, 高沪, 陈琳, 唐发娟, 李熙鸿. 转录因子12过表达对脓毒症相关性脑病大鼠大脑皮质的保护作用及其机制[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 540-549.
[2] 韩李念, 王君. 放射性皮肤损伤治疗的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 533-537.
[3] 陆美琪, 赵洁, 单菲, 王兴蕾, 姜笃银. 药物相关坏疽性脓皮病的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(05): 447-450.
[4] 张潇尹, 于洋. 牙龈卟啉单胞菌介导慢性肾病发生发展的研究进展[J]. 中华口腔医学研究杂志(电子版), 2023, 17(05): 328-334.
[5] 李永浩, 高雪菲, 郭田田, 张进, 张彩针, 刘静. 肥胖合并甲状腺癌相关机制的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(04): 311-315.
[6] 叶晓琳, 刘云飞, 庞明泉, 王海久, 任利, 侯立朝, 于文昊, 王志鑫, 樊海宁. 肝再生细胞来源及调控机制的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 96-99.
[7] 熊风, 林辉煌, 陈晓波. 铥激光在泌尿外科中的临床应用及研究进展[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 533-536.
[8] 唐英俊, 李华娟, 王赛妮, 徐旺, 刘峰, 李羲, 郝新宝, 黄华萍. 人脐带间充质干细胞治疗COPD小鼠及机制分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 476-480.
[9] 任加发, 邬步云, 邢昌赢, 毛慧娟. 2022年急性肾损伤领域基础与临床研究进展[J]. 中华肾病研究电子杂志, 2023, 12(05): 276-281.
[10] 张坤淇, 张睿, 徐佳, 康庆林. 漂浮膝损伤的诊治进展[J]. 中华老年骨科与康复电子杂志, 2023, 09(04): 252-256.
[11] 金刚, 李英真, 施维, 李博. 帕金森病在病理生理学中的研究进展[J]. 中华脑科疾病与康复杂志(电子版), 2023, 13(05): 315-319.
[12] 李田, 徐洪, 刘和亮. 尘肺病的相关研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 900-905.
[13] 沈丘月, 侯新琳. n-3多不饱和脂肪酸脑保护机制研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(04): 471-478.
[14] 尹琛俊, 张喆, 李晓明. 卵圆孔未闭相关血栓形成机制的研究进展[J]. 中华脑血管病杂志(电子版), 2023, 17(04): 307-311.
[15] 于玲, 张祉昱, 张喆, 傅瑜. 偏头痛常见诱因及其在疾病管理中的应用研究进展[J]. 中华脑血管病杂志(电子版), 2023, 17(04): 400-403.
阅读次数
全文


摘要