Research Progress of Anti-Aging Related Targets and Anti-Aging Drugs
YANG Yi-hui, REN Li-wen, ZHENG Xiang-jin, LIU Jin-yi, LI Sha, LI Wan, FU Wei-qi, WANG Jin-hua*, DU Guan-hua*
Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract：Aging is an irreversible process that RESULTS in gradual decline of physiological function with the growth of age. With the progress of research on aging related mechanisms, it has become a hot issue in the field of anti-aging research to find effective anti-aging drugs to delay aging and prolong life by means of drug intervention. In recent years, a series of diverse Compounds from different sources have been found to have potential anti-aging activities, and some of them have entered the stage of clinical trials, which greatly promoted the continuous progress of anti-aging drugs. The concept of aging and its related signaling pathways and targets is introduced, and the advanced research progress of anti-aging drugs in recent years is summarized. Finally, the future development trend of anti-aging study and anti-aging drugs is discussed.
杨艺辉, 任利文, 郑湘锦, 刘金宜, 李莎, 李婉, 富炜琦, 王金华, 杜冠华. 抗衰老靶点及药物的研究进展[J]. 中国药学杂志, 2021, 56(16): 1282-1290.
YANG Yi-hui, REN Li-wen, ZHENG Xiang-jin, LIU Jin-yi, LI Sha, LI Wan, FU Wei-qi, WANG Jin-hua, DU Guan-hua. Research Progress of Anti-Aging Related Targets and Anti-Aging Drugs. Chinese Pharmaceutical Journal, 2021, 56(16): 1282-1290.
QIAN M, LIU B. Pharmaceutical Intervention of Aging[J]. Adv Exp Med Biol, 2018,1086(15): 235-254.
[2]
WYSS-CORAY T. Ageing, neurodegeneration and brain rejuvenation[J]. Nature, 2016, 539(7628):180-186.
[3]
MARTA G-F, DIAZ-RUIZ A, HAUSER D, et al. The road ahead for health and lifespan interventions[J]. Ageing Res Rev, 2020, 59(101037): 1-19.
[4]
GONOS E S, CHONDROGIANNI N, DJORDJEVIC A M. Where ageing goes nowadays: Mechanisms, pathways, biomarkers and anti-ageing strategies[J]. Mech Ageing Dev, 2019, 177 (1):1-3.
[5]
TACUTU R, THORNTON D, JOHNSON E, et al. Human ageing genomic resources: new and updated databases[J]. Nucleic Acids Res, 2018, 46(1):1083-1090.
[6]
SUN X , CHEN W D , WANG Y D. DAF-16/FOXO transcription factor in aging and longevity[J]. Front Pharmacol, 2017, 8(548): 1-8.
[7]
KENYON C, CHANG J, GENSCH E, et al. A C. elegans mutant that lives twice as long as wild type[J]. Nature, 1993, 366(6454): 461-464.
[8]
OGG S, PARADIS S, GOTTLIEB S, et al. The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans[J]. Nature, 1997, 389(6654): 994-999.
[9]
SUN X, CHEN W D, WANG Y D. DAF-16/FOXO Transcription Factor in Aging and Longevity[J]. Front Pharmacol, 2017, 8(548):1-8.
[10]
BRUNET A, BONNI A, ZIGMOND M J, et al. Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor[J]. Cell, 1999, 96(6): 857-868.
[11]
GUARENTE L, KENYON C. Genetic pathways that regulate ageing in model organisms[J]. Nature, 2000, 408(6809): 255-262.
[12]
FABRIZIO P, POZZA F, PLETCHER S D, et al. Regulation of longevity and stress resistance by Sch9 in yeast[J]. Science, 292(5515):288-290.
[13]
CLANCY D J. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein[J]. Science, 2001, 292(5514):104-106.
[14]
TATAR M, KOPELMAN A, EPSTEIN D, et al. A mutant drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function[J]. Science, 2001, 292(5514): 107-110.
[15]
WILLCOX B J, DONLON T A, HE Q, et al. FOXO3A genotype is strongly associated with human longevity[J]. Proc Natl Acad Sci USA, 2008, 105(37): 13987-13992.
[16]
BARTKE A. Impact of reduced insulin-like growth factor-1/insulin signaling on aging in mammals: novel findings[J]. Aging cell, 2008, 7(3): 285-90.
[17]
HEITMAN J, MOVVA N R, HALL M N. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast[J]. Science, 1991, 253(5022): 905-909.
[18]
MANNICK J B, DEL GIUDICE G, LATTANZI M, et al. mTOR inhibition improves immune function in the elderly[J]. Sci Transl Med, 2014, 6(268): 1-7.
[19]
AYLETT C H, SAUER E, IMSENG S, et al. Architecture of human mTOR complex 1[J]. Science, 2016, 351(6268): 48-52.
[20]
WEICHHART T. mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review[J]. Gerontology, 2018, 64(2): 127-134.
[21]
VELLAI T, TAKACS-VELLAI K, ZHANG Y, et al. Genetics: influence of TOR kinase on lifespan in C. elegans[J]. Nature, 2003, 426(6967): 620.
[22]
KAPAHI P, ZID B M, HARPER T, et al. Regulation of lifespan in drosophila by modulation of genes in the TOR signaling pathway[J]. Curr Biol, 2004, 14(10): 885-890.
[23]
KAEBERLEIN M, POWERS R W, 3RD, STEFFEN K K, et al. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients[J]. Science, 2005, 310(5751): 1193-1196.
[24]
WU J J, LIU J, CHEN E B, et al. Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression[J]. Cell Rep, 2013, 4(5): 913-920.
[25]
ZID B M, ROGERS A N, KATEWA S D, et al. 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila[J]. Cell, 2009, 139(1): 149-160.
[26]
HANSEN M, RUBINSZTEIN D C, WALKER D W. Autophagy as a promoter of longevity: insights from model organisms[J]. Nat Rev Mol Cell Biol, 2018, 19(9): 579-593.
[27]
SAXTON R A, SABATINI D M. mTOR signaling in growth metabolism, and disease[J]. Cell, 2017, 168(6): 960-976.
[28]
VASSILOPOULOS A, FRITZ K S, PETERSEN D R, et al. The human sirtuin family: evolutionary divergences and functions[J]. Hum Genomics, 2011, 5(5): 485-496.
[29]
O'CALLAGHAN C, VASSILOPOULOS A. Sirtuins at the crossroads of stemness, aging, and cancer[J]. Aging cell, 2017, 16(6): 1208-1218.
[30]
KAEBERLEIN M, MCVEY M, GUARENTE L. The SIR2/3/4 complex and SIR2 alone promote longevity in saccharomyces cerevisiae by two different mechanisms[J]. Genes Dev, 1999, 13(19): 2570-2580.
[31]
MICHAN S, SINCLAIR D. Sirtuins in mammals: insights into their biological function[J]. Biochem J, 2007, 404(1): 1-13.
[32]
HOUTKOOPER R H, PIRINEN E, AUWERX J. Sirtuins as regulators of metabolism and healthspan[J]. Nat Rev Mol Cell Biol, 2012, 13(4): 225-238.
[33]
BORDONE L, COHEN D, ROBINSON A, et al. SIRT1 transgenic mice show phenotypes resembling calorie restriction[J]. Aging cell, 2007, 6(6): 759-767.
[34]
KANFI Y, NAIMAN S, AMIR G, et al. The sirtuin SIRT6 regulates lifespan in male mice[J]. Nature, 2012, 483(7388): 218-221.
[35]
HEBERT A S, DITTENHAFER-REED K E, YU W, et al. Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome[J]. Molecular cell, 2013, 49(1): 186-199.
[36]
SATOH A, BRACE C S, BEN-JOSEF G, et al. SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus[J]. J Neurosci, 2010, 30(30): 10220-10232.
[37]
TOIBER D, SEBASTIAN C, MOSTOSLAVSKY R. Characterization of nuclear sirtuins: molecular mechanisms and physiological relevance[J]. Handb Exp Pharmacol, 2011, 206(8):189-224.
[38]
GIANNAKOU M E, PARTRIDGE L. The interaction between FOXO and SIRT1: tipping the balance towards survival[J]. Trends Cell Biol, 2004, 14(8): 408-412.
[39]
LUO J, NIKOLAEV A Y, IMAI S, et al. Negative control of p53 by Sir2alpha promotes cell survival under stress[J]. Cell, 2001, 107(2): 137-148.
[40]
BLUM C A, ELLIS J L, LOH C, et al. SIRT1 modulation as a novel approach to the treatment of diseases of aging[J]. J Med Chem, 2011, 54(2): 417-432.
[41]
VERDIN E. NAD in aging, metabolism, and neurodegeneration[J]. Science, 2015, 350(6265): 1208-1213.
[42]
LANDRY J, SUTTON A, TAFROV S T, et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases[J]. Proc Natl Acad Sci U S A, 2000, 97(11): 5807-5811.
[43]
COHEN H Y, MILLER C, BITTERMAN K J, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase[J]. Science, 2004, 305(5682): 390-392.
[44]
MOUCHIROUD L, HOUTKOOPER R H, MOULLAN N, et al. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling[J]. Cell, 2013, 154(2): 430-441.
[45]
HARDIE D G, ROSS F A, HAWLEY S A. AMPK: a nutrient and energy sensor that maintains energy homeostasis[J]. Nat Rev Mol Cell Biol, 2012, 13(4): 251-262.
[46]
XIAO B, SANDERS M J, UNDERWOOD E, et al. Structure of mammalian AMPK and its regulation by ADP[J]. Nature, 2011, 472(7342): 230-233.
[47]
SALMINEN A, KAARNIRANTA K, KAUPPINEN A. Age-related changes in AMPK activation: role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways[J]. Ageing Res Rev, 2016, 28(6):15-26.
[48]
APFELD J, O'CONNOR G, MCDONAGH T, et al. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans[J]. Genes Dev, 2004, 18(24): 3004-3009.
[49]
SALMINEN A, KAARNIRANTA K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network[J]. Ageing Res Rev, 2012, 11(2): 230-241.
[50]
FUNAKOSHI M, TSUDA M, MURAMATSU K, et al. A gain-of-function screen identifies wdb and lkb1 as lifespan-extending genes in Drosophila[J]. Biochem Biophys Res Commun, 2011, 405(4): 667-672.
[51]
MARTIN-MONTALVO A, MERCKEN E M, MITCHELL S J, et al. Metformin improves healthspan and lifespan in mice[J]. Nat Commun, 2013, 4(2192):1-9.
[52]
GORGOULIS V, ADAMS P D, ALIMONTI A, et al. Cellular senescence: defining a path forward[J]. Cell, 2019, 179(4): 813-827.
[53]
AMAYA-MONTOYA M, PÉREZ-LONDOÑO A, GUATIBONZA-GARCíA V, et al. Cellular senescence as a therapeutic target for age-related diseases: a review[J]. Adv Ther, 2020, 37(4): 1407-1424.
[54]
ZHENG W G, QIN X M, GAO L, et al. Research advances in understanding the senescence-associated secretory phenotype and relevant drugs[J]. Acta Pharm Sin(药学学报), 2020, 55(1): 8-14.
[55]
HERNANDEZ-SEGURA A, NEHME J, DEMARIA M. Hallmarks of Cellular Senescence[J]. Trends Cell Biol, 2018, 28(6): 436-453.
[56]
PAEZ-RIBES M, GONZÁLEZ-GUALDA E, DOHERTY G J, et al. Targeting senescent cells in translational medicine[J]. EMBO Mol Med, 2019, 11(12): 1-10.
[57]
CHILDS B G, GLUSCEVIC M, BAKER D J, et al. Senescent cells: an emerging target for diseases of ageing[J]. Nat Rev Drug Discov, 2017, 16(10): 718-735.
[58]
SHAN T J, SUN J, LIANG H H. Progress in the study of association between cellular senescence and organ fibrosis[J]. Acta Pharm Sin(药学学报), 2019, 54(9): 1531-1537.
[59]
BAKER D J, CHILDS B G, DURIK M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan[J]. Nature, 2016, 530(7589): 184-189.
[60]
HE S, SHARPLESS N E. Senescence in health and disease[J]. Cell, 2017, 169(6): 1000-1011.
[61]
ROLT A, COX L S. Structural basis of the anti-ageing effects of polyphenolics: mitigation of oxidative stress[J]. BMC Chem, 2020, 14(50):1-13.
[62]
AGRAWAL M. Natural polyphenols based new therapeutic avenues for advanced biomedical applications[J]. Drug Metab Rev, 2015, 47(4): 420-430.
[63]
WAHAB A, GAO K, JIA C, et al. Significance of resveratrol in clinical management of chronic diseases[J]. Molecules, 2017, 22(1329): 1-19.
[64]
LI Y R, LI S, LIN C C. Effect of resveratrol and pterostilbene on aging and longevity[J]. BioFactors, 2018, 44(1): 69-82.
[65]
ZIA A, FARKHONDEH T, POURBAGHER-SHAHRI A M, et al. The role of curcumin in aging and senescence: molecular mechanisms[J]. Biomed Pharmacother, 2021, 134:111119.
[66]
PIETSCH K, SAUL N, MENZEL R, et al. Quercetin mediated lifespan extension in caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43[J]. Biogerontology, 2009, 10(5): 565-578.
[67]
ALUGOJU P, JANARDHANSHETTY S S, SUBARAMANIAN S, et al. Quercetin protects yeast saccharomyces cerevisiae pep4 mutant from oxidative and apoptotic stress and extends chronological lifespan[J]. Curr Microbiol, 2018, 75(5): 519-530.
[68]
PROSHKINA E, LASHMANOVA E, DOBROVOLSKAYA E, et al. Geroprotective and radioprotective activity of quercetin, (-)-epicatechin, and ibuprofen in drosophila melanogaster[J]. Front Pharmacol, 2016, 7(505): 1-16.
[69]
HICKSON L J, LANGHI PRATA L G P, BOBART S A, et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease[J]. EBioMedicine, 2019, 47: 446-456.
[70]
YOUSEFZADEH M J, ZHU Y, MCGOWAN S J, et al. Fisetin is a senotherapeutic that extends health and lifespan[J]. EBio Medicine, 2018, 36:18-28.
[71]
WANG H, LIU J, LI T, et al. Blueberry extract promotes longevity and stress tolerance via DAF-16 in Caenorhabditis elegans[J]. Food Funct, 2018, 9(10): 5273-5282.
[72]
SONG B, ZHENG B, LI T, et al. Raspberry extract promoted longevity and stress tolerance via the insulin/IGF signaling pathway and DAF-16 in Caenorhabditis elegans[J]. Food Funct, 2020, 11(4): 3598-3609.
[73]
YOO Y J, KIM H, PARK S R, et al. An overview of rapamycin: from discovery to future perspectives[J]. J Ind Microbiol Biotechnol, 2017, 44(4): 537-553.
[74]
CAMPISI J, KAPAHI P, LITHGOW G J, et al. From discoveries in ageing research to therapeutics for healthy ageing[J]. Nature, 2019, 571(7764): 183-192.
[75]
URFER S R, KAEBERLEIN T L, MAILHEAU S, et al. A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs[J]. GeroScience, 2017, 39(2): 117-127.
[76]
SU Y, WANG T, WU N, et al. Alpha-ketoglutarate extends drosophila lifespan by inhibiting mTOR and activating AMPK[J]. Aging, 2019, 11(12): 4183-4197.
[77]
ASADI SHAHMIRZADI A, EDGAR D, LIAO C Y, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice[J]. Cell Metab, 2020, 32(3): 447-456.
[78]
QIAN M, LIU B. Advances in pharmacological interventions of aging in mice[J]. Transl Med Aging, 2019, 3(1):116-120.
[79]
MADEO F, EISENBERG T, PIETROCOLA F, et al. Spermidine in health and disease[J]. Science, 2018, 359(6374): 1-10.
[80]
MADEO F, BAUER M A, CARMONA-GUTIERREZ D, et al. Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?[J]. Autophagy, 2019, 15(1): 165-168.
[81]
BÜCHTER C, ZHAO L, HAVERMANN S, et al. TSG (2, 3, 5, 4'-Tetrahydroxystilbene-2-O-β-D-glucoside) from the Chinese herb Polygonum multiflorum increases life span and stress resistance of Caenorhabditis elegans[J]. Oxid Med Cell Longev, 2015, 2015:124357.
[82]
ZHOU X, YANG Q, XIE Y, et al. Tetrahydroxystilbene glucoside extends mouse life span via upregulating neural klotho and downregulating neural insulin or insulin-like growth factor 1[J]. Neurobiol Aging, 2015, 36(3): 1462-1470.
[83]
CUONG V T, CHEN W, SHI J, et al. The anti-oxidation and anti-aging effects of ganoderma lucidum in caenorhabditis elegans[J]. Exp Gerontol, 2019, 117(3):99-105.
[84]
DANG Y, AN Y, HE J, et al. Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression[J]. Aging cell, 2020, 19(1): e13060.
[85]
SOUKAS A A, HAO H, WU L. Metformin as anti-aging therapy: is it for everyone?[J]. Trends Endocrinol Metab, 2019, 30(10): 745-755.
[86]
KULKARNI A S, GUBBI S, BARZILAI N. Benefits of metformin in attenuating the hallmarks of aging[J]. Cell Metab, 2020, 32(1): 15-30.
[87]
BANNISTER C A, HOLDEN S E, JENKINS-JONES S, et al. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls[J]. Diabetes Obes Metab, 2014, 16(11): 1165-11673.
[88]
KIRKLAND J L, TCHKONIA T. Senolytic drugs: from discovery to translation[J]. J Intern Med, 2020, 288(5): 518-536.
[89]
XU M, PIRTSKHALAVA T, FARR J N, et al. Senolytics improve physical function and increase lifespan in old age[J]. Nat Med, 2018, 24(8): 1246-1256.
[90]
CHING T T, CHIANG W C, CHEN C S, et al. Celecoxib extends C. elegans lifespan via inhibition of insulin-like signaling but not cyclooxygenase-2 activity[J]. Aging cell, 2011, 10(3): 506-519.
[91]
WU Q, LIAN T, FAN X, et al. 2, 5-Dimethyl-celecoxib extends drosophila life span via a mechanism that requires insulin and target of rapamycin signaling[J]. J Gerontol A Biol Sci Med Sci, 2017, 72(10): 1334-1341.
[92]
HANEFELD M, SCHAPER F. Acarbose: oral anti-diabetes drug with additional cardiovascular benefits[J]. Expert Rev Cardiovasc Ther, 2008, 6(2): 153-163.
[93]
DODDS S G, PARIHAR M, JAVORS M, et al. Acarbose improved survival for Apc+/Min mice[J]. Aging cell, 2020, 19(2): e13088.
[94]
YOSEF R, PILPEL N, TOKARSKY-AMIEL R, et al. Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL[J]. Nat Commun, 2016, 7:11190.
[95]
CAI Y, ZHOU H, ZHU Y, et al. Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice[J]. Cell Res, 2020, 30(7): 574-589.
[96]
CASTILLO-QUAN J I, LI L, KINGHORN K J, et al. Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis[J]. Cell Rep, 2016, 15(3): 638-650.
[97]
BAAR M P, BRANDT R M C, PUTAVET D A, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging[J]. Cell, 2017, 169(1): 132-147.
[98]
MÖLLER N P, SCHOLZ-AHRENS K E, ROOS N, et al. Bioactive peptides and proteins from foods: indication for health effects[J]. Eur J Nutr, 2008, 47(4): 171-182.
[99]
BHULLAR K S, WU J. Dietary peptides in aging: evidence and prospects[J]. Food Sci Hum Well(食品科学与人类健康), 2020, 9(1): 1-7.
[100]
SU H L, BAO Y Z, ZHANG J, et al. Protective effects of carnosic acid against aging in a premature cellular senescence model and in a D-galactose induced mouse model[J]. Acta Pharm Sin(药学学报), 2020, 55(5): 915-921.
[101]
RAHIMI V B, ASKARI V R, MOUSAVI S H. Ellagic acid reveals promising anti-aging effects against D-galactose-induced aging on human neuroblastoma cell line, SH-SY5Y: A mechanistic study[J]. Biomed Pharmacother, 2018, 108: 1712-1724.
[102]
KONG S Z, LI J C, LI S D, et al. Anti-aging effect of chitosan oligosaccharide on D-galactose-induced subacute aging in mice[J]. Mar Drugs, 2018, 16(6):1-13.
[103]
BAO X W, LI J Y, REN W, et al. Antioxidant effects of hippophae rhamnoides polysaccharide on aging mouse induced by D-galactose[J]. Sci Tech Food Ind(食品工业科技), 2020, 41(4): 293-297
[104]
TANG Y, ZHU Z Y, LIU Y, et al. The chemical structure and anti-aging bioactivity of an acid polysaccharide obtained from rose buds[J]. Food Funct, 2018, 9(4): 2300-2312.
[105]
FENG S, CHENG H, XU Z, et al. Thermal stress resistance and aging effects of panax notoginseng polysaccharides on caenorhabditis elegans[J]. Int J Biol Macromol, 2015, 81(12): 188-194.
[106]
GUO K, SU L, WANG Y, et al. Antioxidant and anti-aging effects of a sea cucumber protein hydrolyzate and bioinformatic characterization of its composing peptides[J]. Food Funct, 2020, 11(6): 5004-5016.
[107]
KIM S J, BEAK S M, PARK S K. Supplementation with triptolide increases resistance to environmental stressors and lifespan in C. elegans[J]. J Food Sci, 2017, 82(6): 1484-1490.
[108]
WANG E, WINK M. Chlorophyll enhances oxidative stress tolerance in caenorhabditis elegans and extends its lifespan[J]. Peer J, 2016, 4:e1879.
[109]
OH S I, PARK J K, PARK S K. Lifespan extension and increased resistance to environmental stressors by N-acetyl-L-cysteine in caenorhabditis elegans[J]. Clinics, 2015, 70(5): 380-386.
[110]
AYYADEVARA S, BHARILL P, DANDAPAT A, et al. Aspirin inhibits oxidant stress, reduces age-associated functional declines, and extends lifespan of caenorhabditis elegans[J]. Antioxid Redox Signal, 2013, 18(5): 481-490.
[111]
HE C, TSUCHIYAMA S K, NGUYEN Q T, et al. Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import[J]. PLoS Genet, 2014, 10(12): 1-16.
[112]
KAVIANI E, RAHMANI M, KAEIDI A, et al. Protective effect of atorvastatin on D-galactose-induced aging model in mice[J]. Behav Brain Res, 2017, 334(9): 55-60.
[113]
SHEN D, LI H, ZHOU R, et al. Pioglitazone attenuates aging-related disorders in aged apolipoprotein E deficient mice[J]. Exp Gerontol, 2018, 102(2): 101-108.
[114]
ALAVEZ S, VANTIPALLI M C, ZUCKER D J, et al. AmyloiD-binding compounds maintain protein homeostasis during ageing and extend lifespan[J]. Nature, 2011, 472(7342): 226-229.
[115]
SHEN C Y, JIANG J G, YANG L, et al. Anti-ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery[J]. Br J Pharmacol, 2017, 174(11): 1395-1425.
[116]
LI M R, ZHOU Y Z, DU G H, et al. Research progress about the anti-aging effect and mechanism of flavonoids from traditional Chinese medicine[J]. Acta Pharm Sin(药学学报), 2019, 54(8): 1382-1391.
[117]
LUCANIC M, PLUMMER W T, CHEN E, et al. Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects[J]. Nat Commun, 2017, 8:14256.
[118]
FAN X, TAKAHASHI-YANAGA F, MORIMOTO S, et al. Celecoxib and 2,5-dimethyl-celecoxib prevent cardiac remodeling inhibiting Akt-mediated signal transduction in an inherited dilated cardiomyopathy mouse model[J]. J Pharmacol Exp Ther, 2011, 338(1): 2-11.
[119]
MALLIKARJUN V, SWIFT J. Therapeutic manipulation of ageing: repurposing old dogs and discovering new tricks[J]. EBioMedicine, 2016, 14(12):24-31.
[120]
KIRKLAND J L, PETERSON C. Healthspan, translation, and new outcomes for animal studies of aging[J]. J Gerontol A Biol Sci Med Sci, 2009, 64(2): 209-212.
[121]
ZHAVORONKOV A, MAMOSHINA P, VANHAELEN Q, et al. Artificial intelligence for aging and longevity research: recent advances and perspectives[J]. Ageing Res Rev, 2019, 49(1):49-66.
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