Aging and Protein Kinases.
Ataxia- and Rad3-related (ATR)
Ataxia-telangiectasia mutated (ATM)
Base excision repair (BER)
DNA damage
DNA damage response (DDR)
DNA-dependent protein kinase, catalytic subunit (DNA-PKcs)
Insulin-like growth factor signaling (IIS)
Mammalian target of rapamycin complex 1 (mTORC1)
Nucleotide excision repair (NER)
Polo-like kinase-1 (PLK1)
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
16
2
2021
Statut:
ppublish
Résumé
Recently, aging has been tried to be explained with large numbers of theories, but none of them can elucidate the changes occurring in the aging process alone. A unified theory encompassing the mechanisms of genetic factors and repair systems in aging is becoming increasingly required. Almost 37 protein kinases contribute to all processes of aging and senescence. Furthermore, these kinases not only regulate the large number of metabolic pathways related to aging processes, but also control these pathways through 12 checkpoints. Thus, in this chapter, the metabolic targets of protein kinases signal transduction pathways were discussed in terms of the aging perspective under five headings, which are the indispensable stages of the aging process. Although the most popular classical aging theories have been stated as DNA damage theory, mitochondrial theory, free radical theory, and telomere theory, it was concluded that the aging process is controlled by protein kinases regardless of the different theories.
Identifiants
pubmed: 33539011
doi: 10.1007/978-3-030-49844-3_2
doi:
Substances chimiques
Cell Cycle Proteins
0
Protein Kinases
EC 2.7.-
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
35-69Références
Abraham RT. PI 3-kinase related kinases: “big” players in stress-induced signaling pathways. DNA Repair (Amst). 2004;3:883–7. https://doi.org/10.1016/j.dnarep.2004.04.002 .
doi: 10.1016/j.dnarep.2004.04.002
Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell. 2004;117:421–6. https://doi.org/10.1016/s0092-8674(04)00452-0 .
doi: 10.1016/s0092-8674(04)00452-0
pubmed: 15137936
Aguirre V, Uchida T, Yenush L, Davis R, White MF. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. 2000;275:9047–54.
doi: 10.1074/jbc.M002847200
Ansari KI, Ogawa D, Rooj AK, Lawler SE, Krichevsky AM, Johnson MD, Chiocca EA, Bronisz A, Godlewski J. Glucose-based regulation of miR-451/AMPK signaling depends on the OCT1 transcription factor. Cell Rep. 2015;11:902–9. https://doi.org/10.1016/j.celrep.2015.04.016 .
doi: 10.1016/j.celrep.2015.04.016
pubmed: 25937278
pmcid: 4431904
Arat NÖ, Griffith JD. Human Rap1 interacts directly with telomeric DNA and regulates TRF2 localization at the telomere. J Biol Chem. 2012;287:41583–94. https://doi.org/10.1074/jbc.M112.415984 .
doi: 10.1074/jbc.M112.415984
pubmed: 23086976
pmcid: 3516710
Arjumand W, Asiaf A, Ahmad ST. Noncoding RNAs in DNA damage response: opportunities for cancer therapeutics. Methods Mol Biol. 2018;1699:3–21. https://doi.org/10.1007/978-1-4939-7435-1_1 .
doi: 10.1007/978-1-4939-7435-1_1
pubmed: 29086365
Aspuria P-J, Tamanoi F. The Rheb family of GTP-binding proteins. Cell Signal. 2004;16:1105–12. https://doi.org/10.1016/j.cellsig.2004.03.019 .
doi: 10.1016/j.cellsig.2004.03.019
pubmed: 15240005
Babizhayev MA, Vishnyakova KS, Yegorov YE. Oxidative damage impact on aging and age-related diseases: drug targeting of telomere attrition and dynamic telomerase activity flirting with imidazole-containing dipeptides. Recent Pat Drug Deliv Formul. 2014;8:163–92. https://doi.org/10.2174/1872211308666140602125505 .
doi: 10.2174/1872211308666140602125505
pubmed: 24894799
Bai X-Y, Ma Y, Ding R, Fu B, Shi S, Chen X-M. miR-335 and miR-34a promote renal senescence by suppressing mitochondrial antioxidative enzymes. J Am Soc Nephrol. 2011;22:1252–61. https://doi.org/10.1681/ASN.2010040367 .
doi: 10.1681/ASN.2010040367
pubmed: 21719785
pmcid: 3137573
Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120(4):483–95.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33. https://doi.org/10.1016/j.cell.2009.01.002 .
doi: 10.1016/j.cell.2009.01.002
pubmed: 19167326
pmcid: 3794896
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97. https://doi.org/10.1016/s0092-8674(04)00045-5 .
doi: 10.1016/s0092-8674(04)00045-5
Barzilai N, Huffman DM, Muzumdar RH, Bartke A. The critical role of metabolic pathways in aging. Diabetes. 2012;61:1315–22. https://doi.org/10.2337/db11-1300 .
doi: 10.2337/db11-1300
pubmed: 22618766
pmcid: 3357299
Batista LFZ, Artandi SE. Understanding telomere diseases through analysis of patient-derived iPS cells. Curr Opin Genet Dev. 2013;23:526–33. https://doi.org/10.1016/j.gde.2013.07.006 .
doi: 10.1016/j.gde.2013.07.006
pubmed: 23993228
pmcid: 3925063
Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C. Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response. Mol Cell. 2012;46:212–25. https://doi.org/10.1016/j.molcel.2012.01.026 .
doi: 10.1016/j.molcel.2012.01.026
pubmed: 22424773
pmcid: 3565437
Bell SP, Dutta A. DNA replication in eukaryotic cells. Annu Rev Biochem. 2002;71:333–74. https://doi.org/10.1146/annurev.biochem.71.110601.135425 .
doi: 10.1146/annurev.biochem.71.110601.135425
pubmed: 12045100
Bennett CF, Kaeberlein M. The mitochondrial unfolded protein response and increased longevity: cause, consequence, or correlation? Exp Gerontol. 2014;56:142–6. https://doi.org/10.1016/j.exger.2014.02.002 .
doi: 10.1016/j.exger.2014.02.002
pubmed: 24518875
Bensimon A, Schmidt A, Ziv Y, Elkon R, Wang S-Y, Chen DJ, Aebersold R, Shiloh Y. ATM-dependent and -independent dynamics of the nuclear phosphoproteome after DNA damage. Sci Signal. 2010;3:rs3. https://doi.org/10.1126/scisignal.2001034 .
doi: 10.1126/scisignal.2001034
pubmed: 21139141
Betz C, Stracka D, Prescianotto-Baschong C, Frieden M, Demaurex N, Hall MN. Feature article: mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology. Proc Natl Acad Sci U S A. 2013;110:12526–34. https://doi.org/10.1073/pnas.1302455110 .
doi: 10.1073/pnas.1302455110
pubmed: 23852728
pmcid: 3732980
Bhaumik D, Scott GK, Schokrpur S, Patil CK, Orjalo AV, Rodier F, Lithgow GJ, Campisi J. MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging (Albany NY). 2009;1, 402:–411. https://doi.org/10.18632/aging.100042 .
Bianchi A, Smith S, Chong L, Elias P, de Lange T. TRF1 is a dimer and bends telomeric DNA. EMBO J. 1997;16:1785–94. https://doi.org/10.1093/emboj/16.7.1785 .
doi: 10.1093/emboj/16.7.1785
pubmed: 9130722
pmcid: 1169781
Bitto A, Wang AM, Bennett CF, Kaeberlein M. Biochemical genetic pathways that modulate aging in multiple species. Cold Spring Harb Perspect Med. 2015;5 https://doi.org/10.1101/cshperspect.a025114 .
Blackwell TK, Steinbaugh MJ, Hourihan JM, Ewald CY, Isik M. SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free Radic Biol Med. 2015;88:290–301. https://doi.org/10.1016/j.freeradbiomed.2015.06.008 .
doi: 10.1016/j.freeradbiomed.2015.06.008
pubmed: 26232625
pmcid: 4809198
Blenis J. TOR, the gateway to cellular metabolism, cell growth, and disease. Cell. 2017;171:10–3. https://doi.org/10.1016/j.cell.2017.08.019 .
doi: 10.1016/j.cell.2017.08.019
pubmed: 28888322
Boisclair YR, Rhoads RP, Ueki I, Wang J, Ooi GT. The acid-labile subunit (ALS) of the 150 kDa IGF-binding protein complex: an important but forgotten component of the circulating IGF system. J Endocrinol. 2001;170:63–70. https://doi.org/10.1677/joe.0.1700063 .
doi: 10.1677/joe.0.1700063
pubmed: 11431138
Bombarde O, Boby C, Gomez D, Frit P, Giraud-Panis M-J, Gilson E, Salles B, Calsou P. TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends. EMBO J. 2010;29:1573–84. https://doi.org/10.1038/emboj.2010.49 .
doi: 10.1038/emboj.2010.49
pubmed: 20407424
pmcid: 2876953
Bonawitz ND, Shadel GS. Rethinking the mitochondrial theory of aging: the role of mitochondrial gene expression in lifespan determination. Cell Cycle. 2007; 6(13):1574–8. https://doi.org/10.4161/cc.6.13.4457 .
Boonekamp JJ, Bauch C, Mulder E, Verhulst S. Does oxidative stress shorten telomeres? Biol Lett. 2017;13 https://doi.org/10.1098/rsbl.2017.0164 .
Boskovic J, Martinez-Gago J, Mendez-Pertuz M, Buscato A, Martinez-Torrecuadrada JL, Blasco MA. Molecular architecture of full-length TRF1 favors its interaction with DNA. J Biol Chem. 2016;291:21829–35. https://doi.org/10.1074/jbc.M116.744896 .
doi: 10.1074/jbc.M116.744896
pubmed: 27563064
pmcid: 5076849
Braun CJ, Zhang X, Savelyeva I, Wolff S, Moll UM, Schepeler T, Ørntoft TF, Andersen CL, Dobbelstein M. p53-responsive micrornas 192 and 215 are capable of inducing cell cycle arrest. Cancer Res. 2008;68:10094–104. https://doi.org/10.1158/0008-5472.CAN-08-1569 .
doi: 10.1158/0008-5472.CAN-08-1569
pubmed: 19074875
pmcid: 2836584
Breving K, Esquela-Kerscher A. The complexities of microRNA regulation: mirandering around the rules. Int J Biochem Cell Biol. 2010;42:1316–29. https://doi.org/10.1016/j.biocel.2009.09.016 .
doi: 10.1016/j.biocel.2009.09.016
pubmed: 19800023
Brierley EJ, Johnson MA, Lightowlers RN, James OF, Turnbull DM. Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle. Ann Neurol. 1998;43:217–23. https://doi.org/10.1002/ana.410430212 .
doi: 10.1002/ana.410430212
pubmed: 9485063
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96:857–68. https://doi.org/10.1016/s0092-8674(00)80595-4 .
doi: 10.1016/s0092-8674(00)80595-4
pubmed: 10102273
Bucci L, Yani SL, Fabbri C, Bijlsma AY, Maier AB, Meskers CG, Narici MV, Jones DA, McPhee JS, Seppet E, Gapeyeva H, Pääsuke M, Sipilä S, Kovanen V, Stenroth L, Musarò A, Hogrel J-Y, Barnouin Y, Butler-Browne G, Capri M, Franceschi C, Salvioli S. Circulating levels of adipokines and IGF-1 are associated with skeletal muscle strength of young and old healthy subjects. Biogerontology. 2013;14:261–72. https://doi.org/10.1007/s10522-013-9428-5 .
doi: 10.1007/s10522-013-9428-5
pubmed: 23666343
Bürkle A. Physiology and pathophysiology of poly(ADP-ribosyl)ation. BioEssays. 2001;23:795–806. https://doi.org/10.1002/bies.1115 .
doi: 10.1002/bies.1115
pubmed: 11536292
Calado RT, Dumitriu B. Telomere dynamics in mice and humans. Semin Hematol. 2013;50:165–74. https://doi.org/10.1053/j.seminhematol.2013.03.030 .
doi: 10.1053/j.seminhematol.2013.03.030
pubmed: 23956466
pmcid: 3742037
Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8:729–40. https://doi.org/10.1038/nrm2233 .
doi: 10.1038/nrm2233
pubmed: 17667954
Celli GB, de Lange T. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol. 2005;7:712–8. https://doi.org/10.1038/ncb1275 .
doi: 10.1038/ncb1275
pubmed: 15968270
Chang J, Li Y, Huang Y, Lam KSL, Hoo RLC, Wong WT, Cheng KKY, Wang Y, Vanhoutte PM, Xu A. Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway. Diabetes. 2010;59:2949–59. https://doi.org/10.2337/db10-0582 .
doi: 10.2337/db10-0582
pubmed: 20802255
pmcid: 2963556
Chang T-C, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26:745–52. https://doi.org/10.1016/j.molcel.2007.05.010 .
doi: 10.1016/j.molcel.2007.05.010
pubmed: 17540599
pmcid: 1939978
Chiruvella KK, Liang Z, Wilson TE. Repair of double-strand breaks by end joining. Cold Spring Harb Perspect Biol. 2013;5:a012757. https://doi.org/10.1101/cshperspect.a012757 .
doi: 10.1101/cshperspect.a012757
pubmed: 23637284
pmcid: 3632057
Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell. 2010;40:179–204. https://doi.org/10.1016/j.molcel.2010.09.019 .
doi: 10.1016/j.molcel.2010.09.019
pubmed: 20965415
pmcid: 2988877
Cortez D, Guntuku S, Qin J, Elledge SJ. ATR and ATRIP: partners in checkpoint signaling. Science. 2001;294:1713–6. https://doi.org/10.1126/science.1065521 .
doi: 10.1126/science.1065521
pubmed: 11721054
Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378:785–9. https://doi.org/10.1038/378785a0 .
doi: 10.1038/378785a0
pubmed: 8524413
Cullinan SB, Diehl JA. PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem. 2004;279:20108–17. https://doi.org/10.1074/jbc.M314219200 .
doi: 10.1074/jbc.M314219200
pubmed: 14978030
Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA. Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol. 2003;23:7198–209. https://doi.org/10.1128/mcb.23.20.7198-7209.2003 .
doi: 10.1128/mcb.23.20.7198-7209.2003
pubmed: 14517290
pmcid: 230321
Cummings NE, Lamming DW. Regulation of metabolic health and aging by nutrient-sensitive signaling pathways. Mol Cell Endocrinol. 2017;455:13–22. https://doi.org/10.1016/j.mce.2016.11.014 .
doi: 10.1016/j.mce.2016.11.014
pubmed: 27884780
da Costa JP, Vitorino R, Silva GM, Vogel C, Duarte AC, Rocha-Santos T. A synopsis on aging-theories, mechanisms and future prospects. Ageing Res Rev. 2016;29:90–112. https://doi.org/10.1016/j.arr.2016.06.005 .
doi: 10.1016/j.arr.2016.06.005
pubmed: 27353257
pmcid: 5991498
d’Adda di Fagagna F. Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer. 2008;8:512–22. https://doi.org/10.1038/nrc2440 .
doi: 10.1038/nrc2440
pubmed: 18574463
d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003;426:194–8. https://doi.org/10.1038/nature02118 .
doi: 10.1038/nature02118
pubmed: 14608368
Davis AJ, Chen BPC, Chen DJ. DNA-PK: a dynamic enzyme in a versatile DSB repair pathway. DNA Repair (Amst). 2014;17:21–9. https://doi.org/10.1016/j.dnarep.2014.02.020 .
doi: 10.1016/j.dnarep.2014.02.020
de Lange T. How telomeres solve the end-protection problem. Science. 2009;326:948–52. https://doi.org/10.1126/science.1170633 .
doi: 10.1126/science.1170633
pubmed: 19965504
pmcid: 2819049
de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100–10. https://doi.org/10.1101/gad.1346005 .
doi: 10.1101/gad.1346005
pubmed: 16166375
Delacroix S, Wagner JM, Kobayashi M, Yamamoto K, Karnitz LM. The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev. 2007;21:1472–7. https://doi.org/10.1101/gad.1547007 .
doi: 10.1101/gad.1547007
pubmed: 17575048
pmcid: 1891424
Dellago H, Preschitz-Kammerhofer B, Terlecki-Zaniewicz L, Schreiner C, Fortschegger K, Chang MW-F, Hackl M, Monteforte R, Kühnel H, Schosserer M, Gruber F, Tschachler E, Scheideler M, Grillari-Voglauer R, Grillari J, Wieser M. High levels of oncomiR-21 contribute to the senescence-induced growth arrest in normal human cells and its knock-down increases the replicative lifespan. Aging Cell. 2013;12:446–58. https://doi.org/10.1111/acel.12069 .
doi: 10.1111/acel.12069
pubmed: 23496142
pmcid: 3864473
Denchi EL, de Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature. 2007;448:1068–71. https://doi.org/10.1038/nature06065 .
doi: 10.1038/nature06065
pubmed: 17687332
Destefano MA, Jacinto E. Regulation of insulin receptor substrate-1 by mTORC2 (mammalian target of rapamycin complex 2). Biochem Soc Trans. 2013;41:896–901. https://doi.org/10.1042/BST20130018 .
doi: 10.1042/BST20130018
pubmed: 23863152
pmcid: 4881742
Dey N, Das F, Mariappan MM, Mandal CC, Ghosh-Choudhury N, Kasinath BS, Choudhury GG. MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. J Biol Chem. 2011;286:25586–603. https://doi.org/10.1074/jbc.M110.208066 .
doi: 10.1074/jbc.M110.208066
pubmed: 21613227
pmcid: 3138272
Dhahbi JM, Spindler SR, Atamna H, Yamakawa A, Guerrero N, Boffelli D, Mote P, Martin DIK. Deep sequencing identifies circulating mouse miRNAs that are functionally implicated in manifestations of aging and responsive to calorie restriction. Aging (Albany NY). 2013;5:130–41. https://doi.org/10.18632/aging.100540 .
doi: 10.18632/aging.100540
Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garré M, Nuciforo PG, Bensimon A, Maestro R, Pelicci PG, d’Adda di Fagagna F. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature. 2006;444:638–42. https://doi.org/10.1038/nature05327 .
doi: 10.1038/nature05327
pubmed: 17136094
Doksani Y, de Lange T. Telomere-internal double-Strand breaks are repaired by homologous recombination and PARP1/Lig3-dependent end-joining. Cell Rep. 2016;17:1646–56. https://doi.org/10.1016/j.celrep.2016.10.008 .
doi: 10.1016/j.celrep.2016.10.008
pubmed: 27806302
pmcid: 5125555
Donate LE, Blasco MA. Telomeres in cancer and ageing. Philos Trans R Soc Lond B Biol Sci. 2011;366:76–84. https://doi.org/10.1098/rstb.2010.0291 .
doi: 10.1098/rstb.2010.0291
pubmed: 21115533
pmcid: 3001316
Dubinsky AN, Dastidar SG, Hsu CL, Zahra R, Djakovic SN, Duarte S, Esau CC, Spencer B, Ashe TD, Fischer KM, MacKenna DA, Sopher BL, Masliah E, Gaasterland T, Chau BN, Pereira de Almeida L, Morrison BE, La Spada AR. Let-7 coordinately suppresses components of the amino acid sensing pathway to repress mTORC1 and induce autophagy. Cell Metab. 2014;20:626–38. https://doi.org/10.1016/j.cmet.2014.09.001 .
doi: 10.1016/j.cmet.2014.09.001
pubmed: 25295787
pmcid: 4245205
Efeyan A, Zoncu R, Chang S, Gumper I, Snitkin H, Wolfson RL, Kirak O, Sabatini DD, Sabatini DM. Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature. 2013;493:679–83. https://doi.org/10.1038/nature11745 .
doi: 10.1038/nature11745
pubmed: 23263183
Effros RB. Roy Walford and the immunologic theory of aging. Immun Ageing. 2005;2:7. https://doi.org/10.1186/1742-4933-2-7 .
doi: 10.1186/1742-4933-2-7
pubmed: 15850487
pmcid: 1131916
ElInati E, Russell HR, Ojarikre OA, Sangrithi M, Hirota T, de Rooij DG, McKinnon PJ, Turner JMA. DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line. Proc Natl Acad Sci U S A. 2017;114:12536–41. https://doi.org/10.1073/pnas.1712530114 .
doi: 10.1073/pnas.1712530114
pubmed: 29114052
pmcid: 5703310
Ewald CY, Landis JN, Porter Abate J, Murphy CT, Blackwell TK. Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity. Nature. 2015;519:97–101. https://doi.org/10.1038/nature14021 .
doi: 10.1038/nature14021
pubmed: 25517099
Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VD. Regulation of longevity and stress resistance by Sch9 in yeast. Science. 2001;292:288–90. https://doi.org/10.1126/science.1059497 .
doi: 10.1126/science.1059497
pubmed: 11292860
Faraonio R, Salerno P, Passaro F, Sedia C, Iaccio A, Bellelli R, Nappi TC, Comegna M, Romano S, Salvatore G, Santoro M, Cimino F. A set of miRNAs participates in the cellular senescence program in human diploid fibroblasts. Cell Death Differ. 2012;19:713–21. https://doi.org/10.1038/cdd.2011.143 .
doi: 10.1038/cdd.2011.143
pubmed: 22052189
Feldser D, Strong MA, Greider CW. Ataxia telangiectasia mutated (Atm) is not required for telomerase-mediated elongation of short telomeres. Proc Natl Acad Sci U S A. 2006;103:2249–51. https://doi.org/10.1073/pnas.0511143103 .
doi: 10.1073/pnas.0511143103
pubmed: 16467146
pmcid: 1413760
Ferreira MG, Miller KM, Cooper JP. Indecent exposure: when telomeres become uncapped. Mol Cell. 2004;13:7–18. https://doi.org/10.1016/s1097-2765(03)00531-8 .
doi: 10.1016/s1097-2765(03)00531-8
pubmed: 14731390
Fingar DC, Salama S, Tsou C, Harlow E, Blenis J. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 2002;16:1472–87. https://doi.org/10.1101/gad.995802 .
doi: 10.1101/gad.995802
pubmed: 12080086
pmcid: 186342
Finucane OM, Lyons CL, Murphy AM, Reynolds CM, Klinger R, Healy NP, Cooke AA, Coll RC, McAllan L, Nilaweera KN, O’Reilly ME, Tierney AC, Morine MJ, Alcala-Diaz JF, Lopez-Miranda J, O’Connor DP, O’Neill LA, McGillicuddy FC, Roche HM. Monounsaturated fatty acid-enriched high-fat diets impede adipose NLRP3 inflammasome-mediated IL-1β secretion and insulin resistance despite obesity. Diabetes. 2015;64:2116–28. https://doi.org/10.2337/db14-1098 .
doi: 10.2337/db14-1098
pubmed: 25626736
Flynn RL, Centore RC, O’Sullivan RJ, Rai R, Tse A, Songyang Z, Chang S, Karlseder J, Zou L. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature. 2011;471:532–6. https://doi.org/10.1038/nature09772 .
doi: 10.1038/nature09772
pubmed: 21399625
pmcid: 3078637
Fontana L, Klein S. Aging, adiposity, and calorie restriction. JAMA. 2007;297:986–94. https://doi.org/10.1001/jama.297.9.986 .
doi: 10.1001/jama.297.9.986
pubmed: 17341713
Fontana L, Partridge L, Longo VD. Extending healthy life span–from yeast to humans. Science. 2010;328:321–6. https://doi.org/10.1126/science.1172539 .
doi: 10.1126/science.1172539
pubmed: 20395504
pmcid: 3607354
Frank CJ, Hyde M, Greider CW. Regulation of telomere elongation by the cyclin-dependent kinase CDK1. Mol Cell. 2006;24:423–32. https://doi.org/10.1016/j.molcel.2006.10.020 .
doi: 10.1016/j.molcel.2006.10.020
pubmed: 17070718
Frescas D, de Lange T. Binding of TPP1 protein to TIN2 protein is required for POT1a,b protein-mediated telomere protection. J Biol Chem. 2014a;289:24180–7. https://doi.org/10.1074/jbc.M114.592592 .
doi: 10.1074/jbc.M114.592592
pubmed: 25056954
pmcid: 4148849
Frescas D, de Lange T. TRF2-tethered TIN2 can mediate telomere prfotection by TPP1/POT1. Mol Cell Biol. 2014b;34:1349–62. https://doi.org/10.1128/MCB.01052-13 .
doi: 10.1128/MCB.01052-13
pubmed: 24469404
pmcid: 3993560
Freund A, Orjalo AV, Desprez P-Y, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 2010;16:238–46. https://doi.org/10.1016/j.molmed.2010.03.003 .
doi: 10.1016/j.molmed.2010.03.003
pubmed: 20444648
pmcid: 2879478
Freund A, Patil CK, Campisi J. p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 2011;30:1536–48. https://doi.org/10.1038/emboj.2011.69 .
doi: 10.1038/emboj.2011.69
pubmed: 21399611
pmcid: 3102277
Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105. https://doi.org/10.1101/gr.082701.108 .
doi: 10.1101/gr.082701.108
pubmed: 18955434
pmcid: 2612969
Gabriely I, Ma XH, Yang XM, Rossetti L, Barzilai N. Leptin resistance during aging is independent of fat mass. Diabetes. 2002;51:1016–21. https://doi.org/10.2337/diabetes.51.4.1016 .
doi: 10.2337/diabetes.51.4.1016
pubmed: 11916920
Gan X, Wang J, Wang C, Sommer E, Kozasa T, Srinivasula S, Alessi D, Offermanns S, Simon MI, Wu D. PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12. Nat Cell Biol. 2012;14:686–96. https://doi.org/10.1038/ncb2507 .
doi: 10.1038/ncb2507
pubmed: 22609986
pmcid: 3389271
Garcia V, Furuya K, Carr AM. Identification and functional analysis of TopBP1 and its homologs. DNA Repair (Amst). 2005;4:1227–39. https://doi.org/10.1016/j.dnarep.2005.04.001 .
doi: 10.1016/j.dnarep.2005.04.001
García-Beccaria M, Martínez P, Flores JM, Blasco MA. In vivo role of checkpoint kinase 2 in signaling telomere dysfunction. Aging Cell. 2014;13:810–6. https://doi.org/10.1111/acel.12237 .
doi: 10.1111/acel.12237
pubmed: 24920220
pmcid: 4331747
Garinis GA, van der Horst GTJ, Vijg J, Hoeijmakers JHJ. DNA damage and ageing: new-age ideas for an age-old problem. Nat Cell Biol. 2008;10:1241–7. https://doi.org/10.1038/ncb1108-1241 .
doi: 10.1038/ncb1108-1241
pubmed: 18978832
pmcid: 4351702
Garzon R, Calin GA, Croce CM. MicroRNAs in Cancer. Annu Rev Med. 2009;60:167–79. https://doi.org/10.1146/annurev.med.59.053006.104707 .
doi: 10.1146/annurev.med.59.053006.104707
pubmed: 19630570
Gilley D, Tanaka H, Hande MP, Kurimasa A, Li GC, Oshimura M, Chen DJ. DNA-PKcs is critical for telomere capping. Proc Natl Acad Sci U S A. 2001;98:15084–8. https://doi.org/10.1073/pnas.261574698 .
doi: 10.1073/pnas.261574698
pubmed: 11742099
pmcid: 64987
Godlewski J, Nowicki MO, Bronisz A, Nuovo G, Palatini J, De Lay M, Van Brocklyn J, Ostrowski MC, Chiocca EA, Lawler SE. MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell. 2010;37:620–32. https://doi.org/10.1016/j.molcel.2010.02.018 .
doi: 10.1016/j.molcel.2010.02.018
pubmed: 20227367
pmcid: 3125113
Görner W, Durchschlag E, Martinez-Pastor MT, Estruch F, Ammerer G, Hamilton B, Ruis H, Schüller C. Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Genes Dev. 1998;12:586–97. https://doi.org/10.1101/gad.12.4.586 .
doi: 10.1101/gad.12.4.586
pubmed: 9472026
pmcid: 316529
Gottlieb TM, Jackson SP. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 1993;72:131–42. https://doi.org/10.1016/0092-8674(93)90057-w .
doi: 10.1016/0092-8674(93)90057-w
pubmed: 8422676
Grandin N, Bailly A, Charbonneau M. Activation of Mrc1, a mediator of the replication checkpoint, by telomere erosion. Biol Cell. 2005;97:799–814. https://doi.org/10.1042/BC20040526 .
doi: 10.1042/BC20040526
pubmed: 15760303
Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D, Gygi SP, Brunet A. An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol. 2007;17:1646–56. https://doi.org/10.1016/j.cub.2007.08.047 .
doi: 10.1016/j.cub.2007.08.047
pubmed: 17900900
pmcid: 2185793
Grigoriev A, Bonini NM. Age-dependent patterns of microRNA RISC loading. Aging (Albany NY). 2014;6:705–6. https://doi.org/10.18632/aging.100692 .
doi: 10.18632/aging.100692
Grube K, Bürkle A. Poly(ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span. Proc Natl Acad Sci U S A. 1992;89:11759–63. https://doi.org/10.1073/pnas.89.24.11759 .
doi: 10.1073/pnas.89.24.11759
pubmed: 1465394
pmcid: 50636
Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466:835–40. https://doi.org/10.1038/nature09267 .
doi: 10.1038/nature09267
pubmed: 20703300
pmcid: 2990499
Guo X, Deng Y, Lin Y, Cosme-Blanco W, Chan S, He H, Yuan G, Brown EJ, Chang S. Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis. EMBO J. 2007;26:4709–19. https://doi.org/10.1038/sj.emboj.7601893 .
doi: 10.1038/sj.emboj.7601893
pubmed: 17948054
pmcid: 2080807
Hackl M, Brunner S, Fortschegger K, Schreiner C, Micutkova L, Mück C, Laschober GT, Lepperdinger G, Sampson N, Berger P, Herndler-Brandstetter D, Wieser M, Kühnel H, Strasser A, Rinnerthaler M, Breitenbach M, Mildner M, Eckhart L, Tschachler E, Trost A, Bauer JW, Papak C, Trajanoski Z, Scheideler M, Grillari-Voglauer R, Grubeck-Loebenstein B, Jansen-Dürr P, Grillari J. miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging. Aging Cell. 2010;9:291–6. https://doi.org/10.1111/j.1474-9726.2010.00549.x .
doi: 10.1111/j.1474-9726.2010.00549.x
pubmed: 20089119
pmcid: 2848978
Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253–95. https://doi.org/10.1146/annurev.pathol.4.110807.092250 .
doi: 10.1146/annurev.pathol.4.110807.092250
pubmed: 20078221
pmcid: 2866163
Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, Ha SH, Ryu SH, Kim S. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149:410–24. https://doi.org/10.1016/j.cell.2012.02.044 .
doi: 10.1016/j.cell.2012.02.044
pubmed: 22424946
Han X, Liu D, Zhang Y, Li Y, Lu W, Chen J, Songyang Z. Akt regulates TPP1 homodimerization and telomere protection. Aging Cell. 2013;12:1091–9. https://doi.org/10.1111/acel.12137 .
doi: 10.1111/acel.12137
pubmed: 23862686
pmcid: 4051222
Han X, Tai H, Wang X, Wang Z, Zhou J, Wei X, Ding Y, Gong H, Mo C, Zhang J, Qin J, Ma Y, Huang N, Xiang R, Xiao H. AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD(+) elevation. Aging Cell. 2016;15:416–27. https://doi.org/10.1111/acel.12446 .
doi: 10.1111/acel.12446
pubmed: 26890602
pmcid: 4854918
Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol. 2007;8:774–85. https://doi.org/10.1038/nrm2249 .
doi: 10.1038/nrm2249
pubmed: 17712357
Hardy CF, Sussel L, Shore D. A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation. Genes Dev. 1992;6:801–14. https://doi.org/10.1101/gad.6.5.801 .
doi: 10.1101/gad.6.5.801
pubmed: 1577274
Harman D. Free radical involvement in aging. Pathophysiology and therapeutic implications. Drugs Aging. 1993;3:60–80. https://doi.org/10.2165/00002512-199303010-00006 .
doi: 10.2165/00002512-199303010-00006
pubmed: 8453186
Harman D. Free radical theory of aging. Mutat Res. 1992;275:257–66. https://doi.org/10.1016/0921-8734(92)90030-s .
doi: 10.1016/0921-8734(92)90030-s
pubmed: 1383768
Harman D. The aging process. Proc Natl Acad Sci U S A. 1981;78:7124–8. https://doi.org/10.1073/pnas.78.11.7124 .
doi: 10.1073/pnas.78.11.7124
pubmed: 6947277
pmcid: 349208
Harper JW, Elledge SJ. The DNA damage response: ten years after. Mol Cell. 2007;28:739–45. https://doi.org/10.1016/j.molcel.2007.11.015 .
doi: 10.1016/j.molcel.2007.11.015
pubmed: 18082599
Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392–5. https://doi.org/10.1038/nature08221 .
doi: 10.1038/nature08221
pubmed: 19587680
pmcid: 2786175
Hattori H, Janky R, Nietfeld W, Aerts S, Madan Babu M, Venkitaraman AR. p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response. Cell Cycle. 2014;13:2572–86. https://doi.org/10.4161/15384101.2015.942209 .
doi: 10.4161/15384101.2015.942209
pubmed: 25486198
pmcid: 4601526
Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39:199–218. https://doi.org/10.1016/j.tibs.2014.02.002 .
doi: 10.1016/j.tibs.2014.02.002
pubmed: 24647116
pmcid: 24647116
Herranz N, Gallage S, Mellone M, Wuestefeld T, Klotz S, Hanley CJ, Raguz S, Acosta JC, Innes AJ, Banito A, Georgilis A, Montoya A, Wolter K, Dharmalingam G, Faull P, Carroll T, Martínez-Barbera JP, Cutillas P, Reisinger F, Heikenwalder M, Miller RA, Withers D, Zender L, Thomas GJ, Gil J. mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nat Cell Biol. 2015;17:1205–17. https://doi.org/10.1038/ncb3225 .
doi: 10.1038/ncb3225
pubmed: 26280535
pmcid: 4589897
Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 2012;13:89–102. https://doi.org/10.1038/nrm3270 .
doi: 10.1038/nrm3270
pubmed: 22251901
Hori YS, Kuno A, Hosoda R, Horio Y. Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress. PLoS One. 2013;8:e73875. https://doi.org/10.1371/journal.pone.0073875 .
doi: 10.1371/journal.pone.0073875
pubmed: 24040102
pmcid: 3770600
Hu H, Du L, Nagabayashi G, Seeger RC, Gatti RA. ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci U S A. 2010;107:1506–11. https://doi.org/10.1073/pnas.0907763107 .
doi: 10.1073/pnas.0907763107
pubmed: 20080624
pmcid: 2824372
Hu H, Gatti RA. MicroRNAs: new players in the DNA damage response. J Mol Cell Biol. 2011;3:151–8. https://doi.org/10.1093/jmcb/mjq042 .
doi: 10.1093/jmcb/mjq042
pubmed: 21183529
Hu Z, Xia B, Postnikoff SD, Shen Z-J, Tomoiaga AS, Harkness TA, Seol JH, Li W, Chen K, Tyler JK. Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan. Elife. 2018;7 https://doi.org/10.7554/eLife.35551 .
Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J. 2008;412:179–90. https://doi.org/10.1042/BJ20080281 .
doi: 10.1042/BJ20080281
pubmed: 18466115
pmcid: 2735030
Hyun S-Y, Hwang H-I, Hwan H-I, Jang Y-J. Polo-like kinase-1 in DNA damage response. BMB Rep. 2014;47:249–55. https://doi.org/10.5483/bmbrep.2014.47.5.061 .
doi: 10.5483/bmbrep.2014.47.5.061
pubmed: 24667170
pmcid: 4163859
Iliakis G, Murmann T, Soni A. Alternative end-joining repair pathways are the ultimate backup for abrogated classical non-homologous end-joining and homologous recombination repair: implications for the formation of chromosome translocations. Mutat Res Genet Toxicol Environ Mutagen. 2015;793:166–75. https://doi.org/10.1016/j.mrgentox.2015.07.001 .
doi: 10.1016/j.mrgentox.2015.07.001
pubmed: 26520387
Inoki K, Li Y, Xu T, Guan K-L. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003;17:1829–34. https://doi.org/10.1101/gad.1110003 .
doi: 10.1101/gad.1110003
pubmed: 12869586
pmcid: 196227
Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999;13:76–86. https://doi.org/10.1101/gad.13.1.76 .
doi: 10.1101/gad.13.1.76
pubmed: 9887101
pmcid: 316370
Iyama T, Wilson DM. DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst). 2013;12:620–36. https://doi.org/10.1016/j.dnarep.2013.04.015 .
doi: 10.1016/j.dnarep.2013.04.015
Jin Jung K, Hyun Kim D, Kyeong Lee E, Woo Song C, Pal Yu B, Young Chung H. Oxidative stress induces inactivation of protein phosphatase 2A, promoting proinflammatory NF-κB in aged rat kidney. Free Radic Biol Med. 2013;61:206–17. https://doi.org/10.1016/j.freeradbiomed.2013.04.005 .
doi: 10.1016/j.freeradbiomed.2013.04.005
pubmed: 23583701
Jin S, Inoue S, Weaver DT. Functions of the DNA dependent protein kinase. Cancer Surv. 1997;29:221–61.
pubmed: 9338103
Johnson SC, Sangesland M, Kaeberlein M, Rabinovitch PS. Modulating mTOR in aging and health. Interdiscip Top Gerontol. 2015;40:107–27. https://doi.org/10.1159/000364974 .
doi: 10.1159/000364974
pubmed: 25341517
Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Thompson CB. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell. 2005;18:283–93. https://doi.org/10.1016/j.molcel.2005.03.027 .
doi: 10.1016/j.molcel.2005.03.027
pubmed: 15866171
Jossen R, Bermejo R. The DNA damage checkpoint response to replication stress: a game of forks. Front Genet. 2013;4:26. https://doi.org/10.3389/fgene.2013.00026 .
doi: 10.3389/fgene.2013.00026
pubmed: 23493417
pmcid: 3595514
Jung KJ, Lee EK, Kim SJ, Song CW, Maruyama N, Ishigami A, Kim ND, Im D-S, Yu BP, Chung HY. Anti-inflammatory activity of SMP30 modulates NF-κB through protein tyrosine kinase/phosphatase balance. J Mol Med. 2015;93:343–56. https://doi.org/10.1007/s00109-014-1219-1 .
doi: 10.1007/s00109-014-1219-1
pubmed: 25394676
Jung KJ, Lee EK, Yu BP, Chung HY. Significance of protein tyrosine kinase/protein tyrosine phosphatase balance in the regulation of NF-kappaB signaling in the inflammatory process and aging. Free Radic Biol Med. 2009;47:983–91. https://doi.org/10.1016/j.freeradbiomed.2009.07.009 .
doi: 10.1016/j.freeradbiomed.2009.07.009
pubmed: 19596065
Kaeberlein M, Powers RW, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science. 2005;310:1193–6. https://doi.org/10.1126/science.1115535 .
doi: 10.1126/science.1115535
pubmed: 16293764
Kang C, Qin J, Osei W, Hu K. Regulation of protein kinase C-epsilon and its age-dependence. Biochem Biophys Res Commun. 2017;482:1201–6. https://doi.org/10.1016/j.bbrc.2016.12.012 .
doi: 10.1016/j.bbrc.2016.12.012
pubmed: 27919679
Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, Lu T, Yankner BA, Campisi J, Elledge SJ. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science 349, aaa5612. 2015; https://doi.org/10.1126/science.aaa5612 .
Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science. 1999;283:1321–5. https://doi.org/10.1126/science.283.5406.1321 .
doi: 10.1126/science.283.5406.1321
pubmed: 10037601
Karnewar S, Neeli PK, Panuganti D, Kotagiri S, Mallappa S, Jain N, Jerald MK, Kotamraju S. Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: relevance in age-associated vascular dysfunction. Biochim Biophys Acta Mol basis Dis. 2018;1864:1115–28. https://doi.org/10.1016/j.bbadis.2018.01.018 .
doi: 10.1016/j.bbadis.2018.01.018
pubmed: 29366775
Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal. 2013;25:1939–48. https://doi.org/10.1016/j.cellsig.2013.06.007 .
doi: 10.1016/j.cellsig.2013.06.007
pubmed: 23770291
Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG, Nishikura K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science. 2007;315:1137–40. https://doi.org/10.1126/science.1138050 .
doi: 10.1126/science.1138050
pubmed: 17322061
pmcid: 2953418
Keith CT, Schreiber SL. PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science. 1995;270:50–1. https://doi.org/10.1126/science.270.5233.50 .
doi: 10.1126/science.270.5233.50
pubmed: 7569949
Kennedy BK, Lamming DW. The mechanistic target of rapamycin: the grand ConducTOR of metabolism and aging. Cell Metab. 2016;23:990–1003. https://doi.org/10.1016/j.cmet.2016.05.009 .
doi: 10.1016/j.cmet.2016.05.009
pubmed: 27304501
pmcid: 4910876
Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 2007;47:89–116. https://doi.org/10.1146/annurev.pharmtox.46.120604.141046 .
doi: 10.1146/annurev.pharmtox.46.120604.141046
pubmed: 16968214
Kibe T, Zimmermann M, de Lange T. TPP1 blocks an ATR-mediated resection mechanism at telomeres. Mol Cell. 2016;61:236–46. https://doi.org/10.1016/j.molcel.2015.12.016 .
doi: 10.1016/j.molcel.2015.12.016
pubmed: 26778124
pmcid: 4724337
Kim AH, Sasaki T, Chao MV. JNK-interacting protein 1 promotes Akt1 activation. J Biol Chem. 2003;278:29830–6. https://doi.org/10.1074/jbc.M305349200 .
doi: 10.1074/jbc.M305349200
pubmed: 12783873
Kim J-K, Liu J, Hu X, Yu C, Roskamp K, Sankaran B, Huang L, Komives EA, Qiao F. Structural basis for shelterin bridge assembly. Mol Cell. 2017;68:698–714.e5. https://doi.org/10.1016/j.molcel.2017.10.032 .
doi: 10.1016/j.molcel.2017.10.032
pubmed: 29149597
pmcid: 5698806
Kim Sh S, Kaminker P, Campisi J. Telomeres, aging and cancer: in search of a happy ending. Oncogene. 2002;21:503–11. https://doi.org/10.1038/sj.onc.1205077 .
doi: 10.1038/sj.onc.1205077
pubmed: 11850775
Kirkwood TBL. Understanding the odd science of aging. Cell. 2005;120:437–47. https://doi.org/10.1016/j.cell.2005.01.027 .
doi: 10.1016/j.cell.2005.01.027
pubmed: 15734677
Klermund J, Bender K, Luke B. High nutrient levels and TORC1 activity reduce cell viability following prolonged telomere dysfunction and cell cycle arrest. Cell Rep. 2014;9:324–35. https://doi.org/10.1016/j.celrep.2014.08.053 .
doi: 10.1016/j.celrep.2014.08.053
pubmed: 25263563
Konishi A, de Lange T. Cell cycle control of telomere protection and NHEJ revealed by a ts mutation in the DNA-binding domain of TRF2. Genes Dev. 2008;22:1221–30. https://doi.org/10.1101/gad.1634008 .
doi: 10.1101/gad.1634008
pubmed: 18451109
pmcid: 2335317
Kopsidas G, Kovalenko SA, Heffernan DR, Yarovaya N, Kramarova L, Stojanovski D, Borg J, Islam MM, Caragounis A, Linnane AW. Tissue mitochondrial DNA changes. A stochastic system. Ann N Y Acad Sci. 2000;908:226–43. https://doi.org/10.1111/j.1749-6632.2000.tb06650.x .
doi: 10.1111/j.1749-6632.2000.tb06650.x
pubmed: 10911962
Kopsidas G, Kovalenko SA, Kelso JM, Linnane AW. An age-associated correlation between cellular bioenergy decline and mtDNA rearrangements in human skeletal muscle. Mutat Res. 1998;421:27–36. https://doi.org/10.1016/s0027-5107(98)00150-x .
doi: 10.1016/s0027-5107(98)00150-x
pubmed: 9748486
Koutsodontis G, Vasilaki E, Chou W-C, Papakosta P, Kardassis D. Physical and functional interactions between members of the tumour suppressor p53 and the Sp families of transcription factors: importance for the regulation of genes involved in cell-cycle arrest and apoptosis. Biochem J. 2005;389:443–55. https://doi.org/10.1042/BJ20041980 .
doi: 10.1042/BJ20041980
pubmed: 15790310
pmcid: 1175122
Kruk PA, Rampino NJ, Bohr VA. DNA damage and repair in telomeres: relation to aging. Proc Natl Acad Sci U S A. 1995;92:258–62. https://doi.org/10.1073/pnas.92.1.258 .
doi: 10.1073/pnas.92.1.258
pubmed: 7816828
pmcid: 42857
Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev. 2010;24:2463–79. https://doi.org/10.1101/gad.1971610 .
doi: 10.1101/gad.1971610
pubmed: 21078816
pmcid: 2975923
Kuki S, Imanishi T, Kobayashi K, Matsuo Y, Obana M, Akasaka T. Hyperglycemia accelerated endothelial progenitor cell senescence via the activation of p38 mitogen-activated protein kinase. Circ J. 2006;70:1076–81. https://doi.org/10.1253/circj.70.1076 .
doi: 10.1253/circj.70.1076
pubmed: 16864945
Kumagai A, Lee J, Yoo HY, Dunphy WG. TopBP1 activates the ATR-ATRIP complex. Cell. 2006;124:943–55. https://doi.org/10.1016/j.cell.2005.12.041 .
doi: 10.1016/j.cell.2005.12.041
pubmed: 16530042
Kumar R, Sharma A, Kumari A, Gulati A, Padwad Y, Sharma R. Epigallocatechin gallate suppresses premature senescence of preadipocytes by inhibition of PI3K/Akt/mTOR pathway and induces senescent cell death by regulation of Bax/Bcl-2 pathway. Biogerontology. 2019;20:171–89. https://doi.org/10.1007/s10522-018-9785-1 .
doi: 10.1007/s10522-018-9785-1
pubmed: 30456590
Kuosmanen SM, Sihvola V, Kansanen E, Kaikkonen MU, Levonen A-L. MicroRNAs mediate the senescence-associated decline of NRF2 in endothelial cells. Redox Biol. 2018;18:77–83. https://doi.org/10.1016/j.redox.2018.06.007 .
doi: 10.1016/j.redox.2018.06.007
pubmed: 29986211
pmcid: 6037909
Laberge R-M, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, Curran SC, Davalos AR, Wilson-Edell KA, Liu S, Limbad C, Demaria M, Li P, Hubbard GB, Ikeno Y, Javors M, Desprez P-Y, Benz CC, Kapahi P, Nelson PS, Campisi J. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol. 2015;17:1049–61. https://doi.org/10.1038/ncb3195 .
doi: 10.1038/ncb3195
pubmed: 26147250
pmcid: 4691706
Lamming DW. Diminished mTOR signaling: a common mode of action for endocrine longevity factors. Springerplus. 2014;3:735. https://doi.org/10.1186/2193-1801-3-735 .
doi: 10.1186/2193-1801-3-735
pubmed: 25674466
pmcid: 4320218
Lamming DW, Demirkan G, Boylan JM, Mihaylova MM, Peng T, Ferreira J, Neretti N, Salomon A, Sabatini DM, Gruppuso PA. Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2). FASEB J. 2014;28:300–15. https://doi.org/10.1096/fj.13-237743 .
doi: 10.1096/fj.13-237743
pubmed: 24072782
pmcid: 3868844
Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335:1638–43. https://doi.org/10.1126/science.1215135 .
doi: 10.1126/science.1215135
pubmed: 22461615
pmcid: 3324089
Lamming DW, Ye L, Sabatini DM, Baur JA. Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest. 2013;123:980–9. https://doi.org/10.1172/JCI64099 .
doi: 10.1172/JCI64099
pubmed: 23454761
pmcid: 3582126
Lansdorp PM. Repair of telomeric DNA prior to replicative senescence. Mech Ageing Dev. 2000;118:23–34. https://doi.org/10.1016/s0047-6374(00)00151-2 .
doi: 10.1016/s0047-6374(00)00151-2
pubmed: 10989122
Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149:274–93. https://doi.org/10.1016/j.cell.2012.03.017 .
doi: 10.1016/j.cell.2012.03.017
pubmed: 22500797
pmcid: 3331679
Lau AW, Liu P, Inuzuka H, Gao D. SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation. Am J Cancer Res. 2014;4:245–55.
pubmed: 24959379
pmcid: 4065405
Lee J, Kemper JK. Controlling SIRT1 expression by microRNAs in health and metabolic disease. Aging (Albany NY). 2010;2:527–34. https://doi.org/10.18632/aging.100184 .
doi: 10.18632/aging.100184
Lee J, Kumagai A, Dunphy WG. The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. J Biol Chem. 2007;282:28036–44. https://doi.org/10.1074/jbc.M704635200 .
doi: 10.1074/jbc.M704635200
pubmed: 17636252
Lee J, Padhye A, Sharma A, Song G, Miao J, Mo Y-Y, Wang L, Kemper JK. A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition. J Biol Chem. 2010;285:12604–11. https://doi.org/10.1074/jbc.M109.094524 .
doi: 10.1074/jbc.M109.094524
pubmed: 20185821
pmcid: 2857134
Lee J-H, Paull TT. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science. 2005;308:551–4. https://doi.org/10.1126/science.1108297 .
doi: 10.1126/science.1108297
pubmed: 15790808
Lee SS, Bohrson C, Pike AM, Wheelan SJ, Greider CW. ATM kinase is required for telomere elongation in mouse and human cells. Cell Rep. 2015;13:1623–32. https://doi.org/10.1016/j.celrep.2015.10.035 .
doi: 10.1016/j.celrep.2015.10.035
pubmed: 26586427
pmcid: 4663052
Lempiäinen H, Halazonetis TD. Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J. 2009;28:3067–73. https://doi.org/10.1038/emboj.2009.281 .
doi: 10.1038/emboj.2009.281
pubmed: 19779456
pmcid: 2752028
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20. https://doi.org/10.1016/j.cell.2004.12.035 .
doi: 10.1016/j.cell.2004.12.035
pubmed: 15652477
Li N, Muthusamy S, Liang R, Sarojini H, Wang E. Increased expression of miR-34a and miR-93 in rat liver during aging, and their impact on the expression of Mgst1 and Sirt1. Mech Ageing Dev. 2011;132:75–85. https://doi.org/10.1016/j.mad.2010.12.004 .
doi: 10.1016/j.mad.2010.12.004
pubmed: 21216258
Li X, Gao T. mTORC2 phosphorylates protein kinase Cζ to regulate its stability and activity. EMBO Rep. 2014;15:191–8. https://doi.org/10.1002/embr.201338119 .
doi: 10.1002/embr.201338119
pubmed: 24375676
Li Y, Xu W, McBurney MW, Longo VD. SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons. Cell Metab. 2008;8:38–48. https://doi.org/10.1016/j.cmet.2008.05.004 .
doi: 10.1016/j.cmet.2008.05.004
pubmed: 18590691
pmcid: 2822839
Lieber MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010;79:181–211. https://doi.org/10.1146/annurev.biochem.052308.093131 .
doi: 10.1146/annurev.biochem.052308.093131
pubmed: 20192759
pmcid: 3079308
Lieber MR. The mechanism of human nonhomologous DNA end joining. J Biol Chem. 2008;283:1–5. https://doi.org/10.1074/jbc.R700039200 .
doi: 10.1074/jbc.R700039200
pubmed: 17999957
Lin S-J, Kaeberlein M, Andalis AA, Sturtz LA, Defossez P-A, Culotta VC, Fink GR, Guarente L. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature. 2002;418:344–8. https://doi.org/10.1038/nature00829 .
doi: 10.1038/nature00829
pubmed: 12124627
Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993;362:709–15. https://doi.org/10.1038/362709a0 .
doi: 10.1038/362709a0
pubmed: 8469282
Liu D, Xu Y. p53, oxidative stress, and aging. Antioxid Redox Signal. 2011;15:1669–78. https://doi.org/10.1089/ars.2010.3644 .
doi: 10.1089/ars.2010.3644
pubmed: 21050134
pmcid: 3151427
Liu H, Wu H-Y, Wang W-Y, Zhao Z-L, Liu X-Y, Wang L-Y. Regulation of miR-92a on vascular endothelial aging via mediating Nrf2-KEAP1-ARE signal pathway. Eur Rev Med Pharmacol Sci. 2017;21:2734–42.
pubmed: 28678311
Llave C, Xie Z, Kasschau KD, Carrington JC. Cleavage of scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science. 2002;297:2053–6. https://doi.org/10.1126/science.1076311 .
doi: 10.1126/science.1076311
Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J. Rheb binds and regulates the mTOR kinase. Curr Biol. 2005;15:702–13. https://doi.org/10.1016/j.cub.2005.02.053 .
doi: 10.1016/j.cub.2005.02.053
pubmed: 15854902
Longhese MP, Clerici M, Lucchini G. The S-phase checkpoint and its regulation in Saccharomyces cerevisiae. Mutat Res. 2003;532:41–58. https://doi.org/10.1016/j.mrfmmm.2003.08.009 .
doi: 10.1016/j.mrfmmm.2003.08.009
pubmed: 14643428
Lovejoy CA, Cortez D. Common mechanisms of PIKK regulation. DNA Repair (Amst). 2009;8:1004–8. https://doi.org/10.1016/j.dnarep.2009.04.006 .
doi: 10.1016/j.dnarep.2009.04.006
Ludlow AT, Gratidão L, Ludlow LW, Spangenburg EE, Roth SM. Acute exercise activates p38 MAPK and increases the expression of telomere-protective genes in cardiac muscle. Exp Physiol. 2017;102:397–410. https://doi.org/10.1113/EP086189 .
doi: 10.1113/EP086189
pubmed: 28166612
pmcid: 5378631
Ma Y, Schwarz K, Lieber MR. The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps. DNA Repair (Amst). 2005;4:845–51. https://doi.org/10.1016/j.dnarep.2005.04.013 .
doi: 10.1016/j.dnarep.2005.04.013
Madeo F, Zimmermann A, Maiuri MC, Kroemer G. Essential role for autophagy in life span extension. J Clin Invest. 2015;125:85–93. https://doi.org/10.1172/JCI73946 .
doi: 10.1172/JCI73946
pubmed: 25654554
pmcid: 4382258
Manning BD. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol. 2004;167:399–403. https://doi.org/10.1083/jcb.200408161 .
doi: 10.1083/jcb.200408161
pubmed: 15533996
pmcid: 2172491
Maréchal A, Zou L. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol. 2013;5 https://doi.org/10.1101/cshperspect.a012716 .
Martens UM, Chavez EA, Poon SS, Schmoor C, Lansdorp PM. Accumulation of short telomeres in human fibroblasts prior to replicative senescence. Exp Cell Res. 2000;256:291–9. https://doi.org/10.1006/excr.2000.4823 .
doi: 10.1006/excr.2000.4823
pubmed: 10739676
Martin TD, Chen X-W, Kaplan REW, Saltiel AR, Walker CL, Reiner DJ, Der CJ. Ral and Rheb GTPase activating proteins integrate mTOR and GTPase signaling in aging, autophagy, and tumor cell invasion. Mol Cell. 2014;53:209–20. https://doi.org/10.1016/j.molcel.2013.12.004 .
doi: 10.1016/j.molcel.2013.12.004
pubmed: 24389102
pmcid: 3955741
Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007;316:1160–6. https://doi.org/10.1126/science.1140321 .
doi: 10.1126/science.1140321
pubmed: 17525332
Maynard S, Fang EF, Scheibye-Knudsen M, Croteau DL, Bohr VA. DNA damage, DNA repair, aging, and neurodegeneration. Cold Spring Harb Perspect Med. 2015;5 https://doi.org/10.1101/cshperspect.a025130 .
McKerlie M, Lin S, Zhu X-D. ATM regulates proteasome-dependent subnuclear localization of TRF1, which is important for telomere maintenance. Nucleic Acids Res. 2012;40:3975–89. https://doi.org/10.1093/nar/gks035 .
doi: 10.1093/nar/gks035
pubmed: 22266654
pmcid: 3351164
McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD. The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. Cell. 1998;94:363–74. https://doi.org/10.1016/s0092-8674(00)81479-8 .
doi: 10.1016/s0092-8674(00)81479-8
pubmed: 9708738
Medvedik O, Lamming DW, Kim KD, Sinclair DA. MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol. 2007;5:e261. https://doi.org/10.1371/journal.pbio.0050261 .
doi: 10.1371/journal.pbio.0050261
pubmed: 17914901
pmcid: 1994990
Méndez-Pertuz M, Martínez P, Blanco-Aparicio C, Gómez-Casero E, Belen García A, Martínez-Torrecuadrada J, Palafox M, Cortés J, Serra V, Pastor J, Blasco MA. Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun. 2017;8:1278. https://doi.org/10.1038/s41467-017-01329-2 .
doi: 10.1038/s41467-017-01329-2
pubmed: 29097657
pmcid: 5668434
Menghini R, Casagrande V, Cardellini M, Martelli E, Terrinoni A, Amati F, Vasa-Nicotera M, Ippoliti A, Novelli G, Melino G, Lauro R, Federici M. MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation. 2009;120:1524–32. https://doi.org/10.1161/CIRCULATIONAHA.109.864629 .
doi: 10.1161/CIRCULATIONAHA.109.864629
pubmed: 19786632
Menolfi D, Jiang W, Lee BJ, Moiseeva T, Shao Z, Estes V, Frattini MG, Bakkenist CJ, Zha S. Kinase-dead ATR differs from ATR loss by limiting the dynamic exchange of ATR and RPA. Nat Commun. 2018;9:5351. https://doi.org/10.1038/s41467-018-07798-3 .
doi: 10.1038/s41467-018-07798-3
pubmed: 30559436
pmcid: 6297235
Menon S, Dibble CC, Talbott G, Hoxhaj G, Valvezan AJ, Takahashi H, Cantley LC, Manning BD. Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell. 2014;156:771–85. https://doi.org/10.1016/j.cell.2013.11.049 .
doi: 10.1016/j.cell.2013.11.049
pubmed: 24529379
pmcid: 4030681
Mercken EM, Crosby SD, Lamming DW, JeBailey L, Krzysik-Walker S, Villareal DT, Capri M, Franceschi C, Zhang Y, Becker K, Sabatini DM, de Cabo R, Fontana L. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell. 2013;12:645–51. https://doi.org/10.1111/acel.12088 .
doi: 10.1111/acel.12088
pubmed: 23601134
pmcid: 3714316
Miller RA, Harrison DE, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA, Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Strong R. An aging interventions testing program: study design and interim report. Aging Cell. 2007;6:565–75. https://doi.org/10.1111/j.1474-9726.2007.00311.x .
doi: 10.1111/j.1474-9726.2007.00311.x
pubmed: 17578509
Mitterberger MC, Lechner S, Mattesich M, Zwerschke W. Adipogenic differentiation is impaired in replicative senescent human subcutaneous adipose-derived stromal/progenitor cells. J Gerontol A Biol Sci Med Sci. 2014;69:13–24. https://doi.org/10.1093/gerona/glt043 .
doi: 10.1093/gerona/glt043
pubmed: 23657974
Mordes DA, Glick GG, Zhao R, Cortez D. TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev. 2008;22:1478–89. https://doi.org/10.1101/gad.1666208 .
doi: 10.1101/gad.1666208
pubmed: 18519640
pmcid: 2418584
Müllers E, Silva Cascales H, Burdova K, Macurek L, Lindqvist A. Residual Cdk1/2 activity after DNA damage promotes senescence. Aging Cell. 2017;16:575–84. https://doi.org/10.1111/acel.12588 .
doi: 10.1111/acel.12588
pubmed: 28345297
pmcid: 5418196
Muraki K, Murnane JP. The DNA damage response at dysfunctional telomeres, and at interstitial and subtelomeric DNA double-strand breaks. Genes Genet Syst. 2018;92:135–52. https://doi.org/10.1266/ggs.17-00014 .
doi: 10.1266/ggs.17-00014
pubmed: 29162774
Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003;424:277–83. https://doi.org/10.1038/nature01789 .
doi: 10.1038/nature01789
pubmed: 12845331
Nishikura K. A-to-I editing of coding and non-coding RNAs by ADARs. Nat Rev Mol Cell Biol. 2016;17:83–96. https://doi.org/10.1038/nrm.2015.4 .
doi: 10.1038/nrm.2015.4
pubmed: 26648264
North, B.J., Rosenberg, M.A., Jeganathan, K.B., Hafner, A.V., Michan, S., Dai, J., Baker, D.J., Cen, Y., Wu, L.E., Sauve, A.A., van Deursen, J.M., Rosenzweig, A., Sinclair, D.A., 2014. SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J. 33, 1438–1453. https://doi.org/10.15252/embj.201386907 .
Ogi H, Goto GH, Ghosh A, Zencir S, Henry E, Sugimoto K. Requirement of the FATC domain of protein kinase Tel1 for localization to DNA ends and target protein recognition. Mol Biol Cell. 2015;26:3480–8. https://doi.org/10.1091/mbc.E15-05-0259 .
doi: 10.1091/mbc.E15-05-0259
pubmed: 26246601
pmcid: 4591692
Oh H, Wang SC, Prahash A, Sano M, Moravec CS, Taffet GE, Michael LH, Youker KA, Entman ML, Schneider MD. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acad Sci U S A. 2003;100:5378–83. https://doi.org/10.1073/pnas.0836098100 .
doi: 10.1073/pnas.0836098100
pubmed: 12702777
pmcid: 154353
Ohm AM, Affandi T, Reyland ME. EGF receptor and PKCδ kinase activate DNA damage-induced pro-survival and pro-apoptotic signaling via biphasic activation of ERK and MSK1 kinases. J Biol Chem. 2019;294:4488–97. https://doi.org/10.1074/jbc.RA118.006944 .
doi: 10.1074/jbc.RA118.006944
pubmed: 30679314
pmcid: 6433046
Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 2003;13:79–85. https://doi.org/10.1016/s0962-8924(02)00042-9 .
doi: 10.1016/s0962-8924(02)00042-9
pubmed: 12559758
Olive V, Bennett MJ, Walker JC, Ma C, Jiang I, Cordon-Cardo C, Li Q-J, Lowe SW, Hannon GJ, He L. miR-19 is a key oncogenic component of mir-17-92. Genes Dev. 2009;23:2839–49. https://doi.org/10.1101/gad.1861409 .
doi: 10.1101/gad.1861409
pubmed: 20008935
pmcid: 2800084
Olivieri F, Ahtiainen M, Lazzarini R, Pöllänen E, Capri M, Lorenzi M, Fulgenzi G, Albertini MC, Salvioli S, Alen MJ, Kujala UM, Borghetti G, Babini L, Kaprio J, Sipilä S, Franceschi C, Kovanen V, Procopio AD. Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions: a study on postmenopausal monozygotic twin pairs. Aging Cell. 2014;13:850–61. https://doi.org/10.1111/acel.12245 .
doi: 10.1111/acel.12245
pubmed: 25040542
pmcid: 4331762
Osborn AJ, Elledge SJ. Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53. Genes Dev. 2003;17:1755–67. https://doi.org/10.1101/gad.1098303 .
doi: 10.1101/gad.1098303
pubmed: 12865299
pmcid: 196183
Otabe S, Yuan X, Fukutani T, Wada N, Hashinaga T, Nakayama H, Hirota N, Kojima M, Yamada K. Overexpression of human adiponectin in transgenic mice results in suppression of fat accumulation and prevention of premature death by high-calorie diet. Am J Physiol Endocrinol Metab. 2007;293:E210–8. https://doi.org/10.1152/ajpendo.00645.2006 .
doi: 10.1152/ajpendo.00645.2006
pubmed: 17389708
Padmanabhan S, Mukhopadhyay A, Narasimhan SD, Tesz G, Czech MP, Tissenbaum HA. A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. Cell. 2009;136:939–51. https://doi.org/10.1016/j.cell.2009.01.025 .
doi: 10.1016/j.cell.2009.01.025
pubmed: 19249087
pmcid: 2707143
Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–34. https://doi.org/10.1146/annurev.genet.41.110306.130350 .
doi: 10.1146/annurev.genet.41.110306.130350
pubmed: 18680434
Pan Y, Shadel GS. Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density. Aging (Albany NY). 2009;1:131–45. https://doi.org/10.18632/aging.100016 .
doi: 10.18632/aging.100016
Pandey AC, Semon JA, Kaushal D, O’Sullivan RP, Glowacki J, Gimble JM, Bunnell BA. MicroRNA profiling reveals age-dependent differential expression of nuclear factor κB and mitogen-activated protein kinase in adipose and bone marrow-derived human mesenchymal stem cells. Stem Cell Res Ther. 2011;2:49. https://doi.org/10.1186/scrt90 .
doi: 10.1186/scrt90
pubmed: 22169120
pmcid: 3340558
Park H-K, Ahima RS. Leptin signaling. F1000Prime Rep. 2014;6, 73 https://doi.org/10.12703/P6-73 .
Picco V, Coste I, Giraud-Panis M-J, Renno T, Gilson E, Pagès G. ERK1/2/MAPK pathway-dependent regulation of the telomeric factor TRF2. Oncotarget. 2016;7:46615–27. https://doi.org/10.18632/oncotarget.10316 .
doi: 10.18632/oncotarget.10316
pubmed: 27366950
pmcid: 5216822
Prasad KN, Wu M, Bondy SC. Telomere shortening during aging: attenuation by antioxidants and anti-inflammatory agents. Mech Ageing Dev. 2017;164:61–6. https://doi.org/10.1016/j.mad.2017.04.004 .
doi: 10.1016/j.mad.2017.04.004
pubmed: 28431907
Promislow DE. DNA repair and the evolution of longevity: a critical analysis. J Theor Biol. 1994;170:291–300. https://doi.org/10.1006/jtbi.1994.1190 .
doi: 10.1006/jtbi.1994.1190
pubmed: 7996857
Ristow M, Zarse K. How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp Gerontol. 2010;45:410–8. https://doi.org/10.1016/j.exger.2010.03.014 .
doi: 10.1016/j.exger.2010.03.014
pubmed: 20350594
Robert L, Labat-Robert J, Robert AM. Genetic, epigenetic and posttranslational mechanisms of aging. Biogerontology. 2010;11:387–99. https://doi.org/10.1007/s10522-010-9262-y .
doi: 10.1007/s10522-010-9262-y
pubmed: 20157779
Roberts EC, Shapiro PS, Nahreini TS, Pages G, Pouyssegur J, Ahn NG. Distinct cell cycle timing requirements for extracellular signal-regulated kinase and phosphoinositide 3-kinase signaling pathways in somatic cell mitosis. Mol Cell Biol. 2002;22:7226–41. https://doi.org/10.1128/mcb.22.20.7226-7241.2002 .
doi: 10.1128/mcb.22.20.7226-7241.2002
pubmed: 12242299
pmcid: 139798
Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD, Neumann-Haefelin E, Sabatini DM, Blackwell TK. TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab. 2012;15:713–24. https://doi.org/10.1016/j.cmet.2012.04.007 .
doi: 10.1016/j.cmet.2012.04.007
pubmed: 22560223
pmcid: 3348514
Rodier F, Coppé J-P, Patil CK, Hoeijmakers WAM, Muñoz DP, Raza SR, Freund A, Campeau E, Davalos AR, Campisi J. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009;11:973–9. https://doi.org/10.1038/ncb1909 .
doi: 10.1038/ncb1909
pubmed: 19597488
pmcid: 2743561
Ruggiero T, Trabucchi M, Ponassi M, Corte G, Chen C-Y, al-Haj L, Khabar KSA, Briata P, Gherzi R. Identification of a set of KSRP target transcripts upregulated by PI3K-AKT signaling. BMC Mol Biol. 2007;8:28. https://doi.org/10.1186/1471-2199-8-28 .
doi: 10.1186/1471-2199-8-28
pubmed: 17437629
pmcid: 1858702
Ruiz R, Pérez-Villegas EM, Manuel Carrión Á. AMPK function in aging process. Curr Drug Targets. 2016;17:932–41. https://doi.org/10.2174/1389450116666151102095825 .
doi: 10.2174/1389450116666151102095825
pubmed: 26521771
Salminen A, Hyttinen JMT, Kaarniranta K. AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med. 2011a;89:667–76. https://doi.org/10.1007/s00109-011-0748-0 .
doi: 10.1007/s00109-011-0748-0
pubmed: 21431325
Salminen A, Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev. 2012;11:230–41. https://doi.org/10.1016/j.arr.2011.12.005 .
doi: 10.1016/j.arr.2011.12.005
pubmed: 22186033
Salminen A, Kaarniranta K. Control of p53 and NF-κB signaling by WIP1 and MIF: role in cellular senescence and organismal aging. Cell Signal. 2011;23:747–52. https://doi.org/10.1016/j.cellsig.2010.10.012 .
doi: 10.1016/j.cellsig.2010.10.012
pubmed: 20940041
Salminen A, Ojala J, Kaarniranta K. Apoptosis and aging: increased resistance to apoptosis enhances the aging process. Cell Mol Life Sci. 2011b;68:1021–31. https://doi.org/10.1007/s00018-010-0597-y .
doi: 10.1007/s00018-010-0597-y
pubmed: 21116678
Sancar A, Lindsey-Boltz LA, Unsal-Kaçmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39–85. https://doi.org/10.1146/annurev.biochem.73.011303.073723 .
doi: 10.1146/annurev.biochem.73.011303.073723
pubmed: 15189136
Sarthy J, Bae NS, Scrafford J, Baumann P. Human RAP1 inhibits non-homologous end joining at telomeres. EMBO J. 2009;28:3390–9. https://doi.org/10.1038/emboj.2009.275 .
doi: 10.1038/emboj.2009.275
pubmed: 19763083
pmcid: 2776107
Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168:960–76. https://doi.org/10.1016/j.cell.2017.02.004 .
doi: 10.1016/j.cell.2017.02.004
pubmed: 28283069
pmcid: 5394987
Schneider A, Dhahbi JM, Atamna H, Clark JP, Colman RJ, Anderson RM. Caloric restriction impacts plasma microRNAs in rhesus monkeys. Aging Cell. 2017;16:1200–3. https://doi.org/10.1111/acel.12636 .
doi: 10.1111/acel.12636
pubmed: 28677323
pmcid: 5595684
Schumacher B, Garinis GA, Hoeijmakers JHJ. Age to survive: DNA damage and aging. Trends Genet. 2008;24:77–85. https://doi.org/10.1016/j.tig.2007.11.004 .
doi: 10.1016/j.tig.2007.11.004
pubmed: 18192065
Selman C, Tullet JMA, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, Woods A, Robinson ICA, Schuster E, Batterham RL, Kozma SC, Thomas G, Carling D, Okkenhaug K, Thornton JM, Partridge L, Gems D, Withers DJ. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science. 2009;326:140–4. https://doi.org/10.1126/science.1177221 .
doi: 10.1126/science.1177221
pubmed: 19797661
pmcid: 4954603
Shah OJ, Wang Z, Hunter T. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr Biol. 2004;14:1650–6. https://doi.org/10.1016/j.cub.2004.08.026 .
doi: 10.1016/j.cub.2004.08.026
pubmed: 15380067
Shay JW, Wright WE. Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis. 2005;26:867–74. https://doi.org/10.1093/carcin/bgh296 .
doi: 10.1093/carcin/bgh296
pubmed: 15471900
Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer. 2003;3:155–68. https://doi.org/10.1038/nrc1011 .
doi: 10.1038/nrc1011
pubmed: 12612651
Shimobayashi M, Hall MN. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat Rev Mol Cell Biol. 2014;15:155–62. https://doi.org/10.1038/nrm3757 .
doi: 10.1038/nrm3757
pubmed: 24556838
Shore D. RAP1: a protean regulator in yeast. Trends Genet. 1994;10:408–12. https://doi.org/10.1016/0168-9525(94)90058-2 .
doi: 10.1016/0168-9525(94)90058-2
pubmed: 7809947
Sirbu BM, Cortez D. DNA damage response: three levels of DNA repair regulation. Cold Spring Harb Perspect Biol. 2013;5:a012724. https://doi.org/10.1101/cshperspect.a012724 .
doi: 10.1101/cshperspect.a012724
pubmed: 23813586
pmcid: 3721278
Smolka MB, Albuquerque CP, Chen S, Zhou H. Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Proc Natl Acad Sci U S A. 2007;104:10364–9. https://doi.org/10.1073/pnas.0701622104 .
doi: 10.1073/pnas.0701622104
pubmed: 17563356
pmcid: 1965519
Sofer A, Lei K, Johannessen CM, Ellisen LW. Regulation of mTOR and cell growth in response to energy stress by REDD1. Mol Cell Biol. 2005;25:5834–45. https://doi.org/10.1128/MCB.25.14.5834-5845.2005 .
doi: 10.1128/MCB.25.14.5834-5845.2005
pubmed: 15988001
pmcid: 1168803
Solari F, Bourbon-Piffaut A, Masse I, Payrastre B, Chan AM-L, Billaud M. The human tumour suppressor PTEN regulates longevity and dauer formation in Caenorhabditis elegans. Oncogene. 2005;24:20–7. https://doi.org/10.1038/sj.onc.1207978 .
doi: 10.1038/sj.onc.1207978
pubmed: 15637588
Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005;9:59–71. https://doi.org/10.1111/j.1582-4934.2005.tb00337.x .
doi: 10.1111/j.1582-4934.2005.tb00337.x
pubmed: 15784165
pmcid: 6741304
Speakman JR, Mitchell SE. Caloric restriction. Mol Aspects Med. 2011;32:159–221. https://doi.org/10.1016/j.mam.2011.07.001 .
doi: 10.1016/j.mam.2011.07.001
pubmed: 21840335
Stanfel MN, Shamieh LS, Kaeberlein M, Kennedy BK. The TOR pathway comes of age. Biochim Biophys Acta. 2009;1790:1067–74. https://doi.org/10.1016/j.bbagen.2009.06.007 .
doi: 10.1016/j.bbagen.2009.06.007
pubmed: 19539012
pmcid: 3981532
Stern B, Nurse P. A quantitative model for the cdc2 control of S phase and mitosis in fission yeast. Trends Genet. 1996;12:345–50.
doi: 10.1016/S0168-9525(96)80016-3
Sui J, Lin Y-F, Xu K, Lee K-J, Wang D, Chen BPC. DNA-PKcs phosphorylates hnRNP-A1 to facilitate the RPA-to-POT1 switch and telomere capping after replication. Nucleic Acids Res. 2015;43:5971–83. https://doi.org/10.1093/nar/gkv539 .
doi: 10.1093/nar/gkv539
pubmed: 25999341
pmcid: 4499152
Sun X, Chen W-D, Wang Y-D. DAF-16/FOXO transcription factor in aging and longevity. Front Pharmacol. 2017;8:548. https://doi.org/10.3389/fphar.2017.00548 .
doi: 10.3389/fphar.2017.00548
pubmed: 28878670
pmcid: 5572328
Swaffer MP, Jones AW, Flynn HR, Snijders AP, Nurse P. CDK substrate phosphorylation and ordering the cell cycle. Cell. 2016;167:1750–1761.e16. https://doi.org/10.1016/j.cell.2016.11.034 .
doi: 10.1016/j.cell.2016.11.034
pubmed: 27984725
pmcid: 5161751
Takai KK, Kibe T, Donigian JR, Frescas D, de Lange T. Telomere protection by TPP1/POT1 requires tethering to TIN2. Mol Cell. 2011;44:647–59. https://doi.org/10.1016/j.molcel.2011.08.043 .
doi: 10.1016/j.molcel.2011.08.043
pubmed: 22099311
pmcid: 3222871
Takano A, Usui I, Haruta T, Kawahara J, Uno T, Iwata M, Kobayashi M. Mammalian target of rapamycin pathway regulates insulin signaling via subcellular redistribution of insulin receptor substrate 1 and integrates nutritional signals and metabolic signals of insulin. Mol Cell Biol. 2001;21:5050–62. https://doi.org/10.1128/MCB.21.15.5050-5062.2001 .
doi: 10.1128/MCB.21.15.5050-5062.2001
pubmed: 11438661
pmcid: 87231
Tan P, Wang Y-J, Li S, Wang Y, He J-Y, Chen Y-Y, Deng H-Q, Huang W, Zhan J-K, Liu Y-S. The PI3K/Akt/mTOR pathway regulates the replicative senescence of human VSMCs. Mol Cell Biochem. 2016;422:1–10. https://doi.org/10.1007/s11010-016-2796-9 .
doi: 10.1007/s11010-016-2796-9
pubmed: 27619662
Testa G, Biasi F, Poli G, Chiarpotto E. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr Pharm Des. 2014;20:2950–77. https://doi.org/10.2174/13816128113196660699 .
doi: 10.2174/13816128113196660699
pubmed: 24079773
Ting NSY, Pohorelic B, Yu Y, Lees-Miller SP, Beattie TL. The human telomerase RNA component, hTR, activates the DNA-dependent protein kinase to phosphorylate heterogeneous nuclear ribonucleoprotein A1. Nucleic Acids Res. 2009;37:6105–15. https://doi.org/10.1093/nar/gkp636 .
doi: 10.1093/nar/gkp636
pubmed: 19656952
pmcid: 2764450
Tong AS, Stern JL, Sfeir A, Kartawinata M, de Lange T, Zhu X-D, Bryan TM. ATM and ATR signaling regulate the recruitment of human telomerase to telomeres. Cell Rep. 2015;13:1633–46. https://doi.org/10.1016/j.celrep.2015.10.041 .
doi: 10.1016/j.celrep.2015.10.041
pubmed: 26586433
pmcid: 4662887
Tosato M, Zamboni V, Ferrini A, Cesari M. The aging process and potential interventions to extend life expectancy. Clin Interv Aging. 2007;2:401–12.
pubmed: 18044191
pmcid: 2685272
Trovesi C, Manfrini N, Falcettoni M, Longhese MP. Regulation of the DNA damage response by cyclin-dependent kinases. J Mol Biol. 2013;425:4756–66. https://doi.org/10.1016/j.jmb.2013.04.013 .
doi: 10.1016/j.jmb.2013.04.013
pubmed: 23603016
Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, Thomas G. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature. 2004;431:200–5. https://doi.org/10.1038/nature02866 .
doi: 10.1038/nature02866
pubmed: 15306821
Uruno A, Yagishita Y, Yamamoto M. The Keap1-Nrf2 system and diabetes mellitus. Arch Biochem Biophys. 2015;566:76–84. https://doi.org/10.1016/j.abb.2014.12.012 .
doi: 10.1016/j.abb.2014.12.012
pubmed: 25528168
van Heemst D. Insulin, IGF-1 and longevity. Aging Dis. 2010;1:147–57.
pubmed: 22396862
pmcid: 3295030
van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998;92:401–13. https://doi.org/10.1016/s0092-8674(00)80932-0 .
doi: 10.1016/s0092-8674(00)80932-0
pubmed: 9476899
Vasa-Nicotera M, Chen H, Tucci P, Yang AL, Saintigny G, Menghini R, Mahè C, Agostini M, Knight RA, Melino G, Federici M. miR-146a is modulated in human endothelial cell with aging. Atherosclerosis. 2011;217:326–30. https://doi.org/10.1016/j.atherosclerosis.2011.03.034 .
doi: 10.1016/j.atherosclerosis.2011.03.034
pubmed: 21511256
Victoria B, Nunez Lopez YO, Masternak MM. MicroRNAs and the metabolic hallmarks of aging. Mol Cell Endocrinol. 2017;455:131–47. https://doi.org/10.1016/j.mce.2016.12.021 .
doi: 10.1016/j.mce.2016.12.021
pubmed: 28062199
pmcid: 5724961
von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci. 2002;27:339–44. https://doi.org/10.1016/s0968-0004(02)02110-2 .
doi: 10.1016/s0968-0004(02)02110-2
Vorovich E, Ratovitski EA. Dual regulation of TERT activity through transcription and splicing by DeltaNP63alpha. Aging (Albany NY). 2008;1:58–67. https://doi.org/10.18632/aging.100003 .
doi: 10.18632/aging.100003
Wakida T, Ikura M, Kuriya K, Ito S, Shiroiwa Y, Habu T, Kawamoto T, Okumura K, Ikura T, Furuya K. The CDK-PLK1 axis targets the DNA damage checkpoint sensor protein RAD9 to promote cell proliferation and tolerance to genotoxic stress. elife. 2017;6 https://doi.org/10.7554/eLife.29953 .
Wallace DC. Mitochondrial diseases in man and mouse. Science. 1999;283:1482–8. https://doi.org/10.1126/science.283.5407.1482 .
doi: 10.1126/science.283.5407.1482
pubmed: 10066162
Wan G, Mathur R, Hu X, Zhang X, Lu X. miRNA response to DNA damage. Trends Biochem Sci. 2011;36:478–84. https://doi.org/10.1016/j.tibs.2011.06.002 .
doi: 10.1016/j.tibs.2011.06.002
pubmed: 21741842
pmcid: 3532742
Wang C, Mao X, Wang L, Liu M, Wetzel MD, Guan K-L, Dong LQ, Liu F. Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1. J Biol Chem. 2007a;282:7991–6. https://doi.org/10.1074/jbc.M700098200 .
doi: 10.1074/jbc.M700098200
pubmed: 17244624
Wang F, Nguyen M, Qin FX-F, Tong Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell. 2007b;6:505–14. https://doi.org/10.1111/j.1474-9726.2007.00304.x .
doi: 10.1111/j.1474-9726.2007.00304.x
pubmed: 17521387
Watanabe R, Tambe Y, Inoue H, Isono T, Haneda M, Isobe K-I, Kobayashi T, Hino O, Okabe H, Chano T. GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress. Int J Mol Med. 2007;19:475–83.
pubmed: 17273797
Wei M, Fabrizio P, Hu J, Ge H, Cheng C, Li L, Longo VD. Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet. 2008;4:e13. https://doi.org/10.1371/journal.pgen.0040013 .
doi: 10.1371/journal.pgen.0040013
pubmed: 18225956
pmcid: 2213705
Weichhart T. mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review. Gerontology. 2018;64:127–34. https://doi.org/10.1159/000484629 .
doi: 10.1159/000484629
pubmed: 29190625
Wellinger RJ, Zakian VA. Everything you ever wanted to know about Saccharomyces cerevisiae telomeres: beginning to end. Genetics. 2012;191:1073–105. https://doi.org/10.1534/genetics.111.137851 .
doi: 10.1534/genetics.111.137851
pubmed: 22879408
pmcid: 3415994
Whitney ML, Jefferson LS, Kimball SR. ATF4 is necessary and sufficient for ER stress-induced upregulation of REDD1 expression. Biochem Biophys Res Commun. 2009;379:451–5. https://doi.org/10.1016/j.bbrc.2008.12.079 .
doi: 10.1016/j.bbrc.2008.12.079
pubmed: 19114033
Williams J, Smith F, Kumar S, Vijayan M, Reddy PH. Are microRNAs true sensors of ageing and cellular senescence? Ageing res. Rev. 2017;35:350–63. https://doi.org/10.1016/j.arr.2016.11.008 .
doi: 10.1016/j.arr.2016.11.008
Wotton D, Shore D. A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes Dev. 1997;11:748–60. https://doi.org/10.1101/gad.11.6.748 .
doi: 10.1101/gad.11.6.748
pubmed: 9087429
Wu Y, Xiao S, Zhu X-D. MRE11-RAD50-NBS1 and ATM function as co-mediators of TRF1 in telomere length control. Nat Struct Mol Biol. 2007;14:832–40. https://doi.org/10.1038/nsmb1286 .
doi: 10.1038/nsmb1286
pubmed: 17694070
Wyman C, Kanaar R. DNA double-strand break repair: all’s well that ends well. Annu Rev Genet. 2006;40:363–83. https://doi.org/10.1146/annurev.genet.40.110405.090451 .
doi: 10.1146/annurev.genet.40.110405.090451
pubmed: 16895466
Xu Y, Lai E, Liu J, Lin J, Yang C, Jia C, Li Y, Bai X, Li M. IKK interacts with rictor and regulates mTORC2. Cell Signal. 2013;25:2239–45. https://doi.org/10.1016/j.cellsig.2013.07.008 .
doi: 10.1016/j.cellsig.2013.07.008
pubmed: 23872070
Yamaguchi S, Ishihara H, Yamada T, Tamura A, Usui M, Tominaga R, Munakata Y, Satake C, Katagiri H, Tashiro F, Aburatani H, Tsukiyama-Kohara K, Miyazaki J, Sonenberg N, Oka Y. ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Cell Metab. 2008;7:269–76. https://doi.org/10.1016/j.cmet.2008.01.008 .
doi: 10.1016/j.cmet.2008.01.008
pubmed: 18316032
Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA. 2008;105:13421–6. https://doi.org/10.1073/pnas.0801613105 .
doi: 10.1073/pnas.0801613105
pubmed: 18755897
Yan H, Xue G, Mei Q, Wang Y, Ding F, Liu M-F, Lu M-H, Tang Y, Yu H, Sun S. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J. 2009;28:2719–32. https://doi.org/10.1038/emboj.2009.214 .
doi: 10.1038/emboj.2009.214
pubmed: 19696742
pmcid: 2750010
Yannone SM, Khan IS, Zhou R-Z, Zhou T, Valerie K, Povirk LF. Coordinate 5′ and 3′ endonucleolytic trimming of terminally blocked blunt DNA double-strand break ends by Artemis nuclease and DNA-dependent protein kinase. Nucleic Acids Res. 2008;36:3354–65. https://doi.org/10.1093/nar/gkn205 .
doi: 10.1093/nar/gkn205
pubmed: 18440975
pmcid: 2425473
Yu JM, Wu X, Gimble JM, Guan X, Freitas MA, Bunnell BA. Age-related changes in mesenchymal stem cells derived from rhesus macaque bone marrow. Aging Cell. 2011;10:66–79. https://doi.org/10.1111/j.1474-9726.2010.00646.x .
doi: 10.1111/j.1474-9726.2010.00646.x
pubmed: 20969724
pmcid: 4339051
Zhang Xinbo, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011;1813:1978–86. https://doi.org/10.1016/j.bbamcr.2011.03.010 .
Zhang Xinna, Wan G, Berger FG, He X, Lu X. The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol Cell. 2011;41:371–83. https://doi.org/10.1016/j.molcel.2011.01.020 .
Zhou S, Greenberger JS, Epperly MW, Goff JP, Adler C, Leboff MS, Glowacki J. Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell. 2008;7:335–43. https://doi.org/10.1111/j.1474-9726.2008.00377.x .
doi: 10.1111/j.1474-9726.2008.00377.x
pubmed: 18248663
pmcid: 2398731
Zhu H, Shyh-Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI, DIAGRAM Consortium, MAGIC Investigators, Altshuler D, Daley GQ. The Lin28/let-7 axis regulates glucose metabolism. Cell. 2011;147:81–94. https://doi.org/10.1016/j.cell.2011.08.033 .
doi: 10.1016/j.cell.2011.08.033
pubmed: 21962509
pmcid: 3353524
Zou L, Elledge SJ. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science. 2003;300:1542–8. https://doi.org/10.1126/science.1083430 .
doi: 10.1126/science.1083430
pubmed: 12791985