Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and Disease    2017, Vol. 8 Issue (5) : 628-642     DOI: 10.14336/AD.2017.0103
Review |
The Biology of Aging and Cancer: A Brief Overview of Shared and Divergent Molecular Hallmarks
Jan R. Aunan1,2,*,William C Cho3,Kjetil Søreide1,2,4,*
1Gastrointestinal Translational Research Unit, Molecular Lab, Stavanger University Hospital, Stavanger, Norway
2Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
3Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
4Department of Clinical Medicine, University of Bergen, Bergen, Norway
Download: PDF(1005 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Aging is the inevitable time-dependent decline in physiological organ function and is a major risk factor for cancer development. Due to advances in health care, hygiene control and food availability, life expectancy is increasing and the population in most developed countries is shifting to an increasing proportion of people at a cancer susceptible age. Mechanisms of aging are also found to occur in carcinogenesis, albeit with shared or divergent end-results. It is now clear that aging and cancer development either share or diverge in several disease mechanisms. Such mechanisms include the role of genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, decreased nutrient sensing and altered metabolism, but also cellular senescence and stem cell function. Cancer cells and aged cells are also fundamentally opposite, as cancer cells can be thought of as hyperactive cells with advantageous mutations, rapid cell division and increased energy consumption, while aged cells are hypoactive with accumulated disadvantageous mutations, cell division inability and a decreased ability for energy production and consumption. Nonetheless, aging and cancer are tightly interconnected and many of the same strategies and drugs may be used to target both, while in other cases antagonistic pleiotrophy come into effect and inhibition of one can be the activation of the other. Cancer can be considered an aging disease, though the shared mechanisms underpinning the two processes remain unclear. Better understanding of the shared and divergent pathways of aging and cancer is needed.

Keywords aging      cancer      genomic instability      epigenetic      telomere      stem cells      genomic instability      metabolism     
Corresponding Authors: Jan R. Aunan,Kjetil Søreide   
Just Accepted Date: 06 January 2017   Issue Date: 27 September 2017
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Jan R. Aunan
William C Cho
Kjetil Søreide
Cite this article:   
Jan R. Aunan,William C Cho,Kjetil Søreide. The Biology of Aging and Cancer: A Brief Overview of Shared and Divergent Molecular Hallmarks[J]. A&D, 2017, 8(5): 628-642.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2017.0103     OR     http://www.aginganddisease.org/EN/Y2017/V8/I5/628
FeatureAgingCancer
Genomic instabilityIncreasedIncreased
Telomere attritionShortened telomeresShortened telomeres but telomerase activation
Epigenetic alteration:
DNA methylationGlobal hypomethylationHyper- of tumor suppressors and hypo- of oncogenes
Histone modification Non-coding DNAComplexmiRNA deregulation; for example, miR17-92 downregulationComplex miRNA deregulation, for example, miR-17-92 upregulation
Proteostasis:
ChaperoningImpairedAugmented
Proteasome activityImpairedAugmented
Autophagy-lysosome activityImpairedAugmented
Deregulated nutrient sensingInhibition of insulin and mTOR signaling increase lifespanInhibition of insulin and mTOR signaling is antineoplastic
Cellular senescenceIncreasedPrevalent in premalignant tumors but evaded in fully malignant tumors
Stem cellExhaustedPotential nidus for tumorigenesis
Table 1  Hallmarks that are either shared or divergent in aging and cancer.
Figure 1.  Lifelong interplay between stem cells in aging and cancer

A simplified model that views aging and cancer from the perspective of alterations within the stem and progenitor cell pool. Over the lifespan of an organism, long-lived cells (such as stem cells) accumulate DNA damage from a number of stresses including intracellular oxidants generated from normal metabolism. The default pathway for such damaged stem cells is to undergo growth arrest, apoptosis or senescence. As more and more stem cells withdraw from the proliferative pool, there is a decrease in the overall number and/or functionality of both stem and progenitor cells. This decrease predisposes the organism to impaired tissue homeostasis and regenerative capacity and could contribute to aging and age-related pathologies. Presumably, some rare cells can escape from this normal default pathway by acquiring additional mutations that allow them to continue to proliferate even in the setting of damaged DNA. These proliferating but damaged cells might provide the seeds for future malignancies. In this scenario, both cancer and aging result primarily from accumulating damage to the stem and progenitor cell compartment. Mutations that allow stem cells to continue to proliferate in the setting of normal growth arrest signals such as DNA damage (for example, loss of p16INK4a or reactivation of telomerase) would temporarily expand the stem cell pool and hence delay age-related pathologies. Over the long term, these mutations would also increase the likelihood of cancer.

During normal aging, stem cells accumulate damage and subsequent stress-dependent changes, for example, de-repression of the CDKN2a (p16INK4a/ARF) locus or telomere shortening. This leads to the increasing abundance of senescent cells (large hexagonal cells) within differentiated tissues. Preneoplastic leasions, arising directly from stem cells or from more committed cells, undergo rapid proliferation (small cells marked with asterisks). These pre-malignant tumor cells rapidly accumulate damage, in part owing to the presence of oncogenes, leading to a higher proportion of tumor cells becoming senescent (cells marked as hexagons filled with white color). Tumor progression to full malignancy is favoured when tumor cells acquire mutations that impair the senescence program (for example, mutations in Trp53 or CDKN2a).

Illustration is modified and based upon Finkel T, Serrano M, Blasco MA. The common biology of cancer and aging. Nature. 2007 Aug 16;448(7155):767-74. Copyright © 2007.

Figure 2.  The dual role of autophagy in cancer

Examples of mechanisms that are related to either tumor suppression or tumor growth where autophagy plays a role. Cx denotes chemotherapy, Rx denotes radioationtherapy.

[1] Siegel RL, Miller KD, Jemal A (2015). Cancer statistics, 2015. CA Cancer J Clin, 65: 5-29
http://dx.doi.org/10.3322/caac.21254
[2] Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013). The hallmarks of aging. Cell, 153: 1194-1217
http://118.145.16.217/magsci/article/article?id=19655884
[3] Moskalev AA, Shaposhnikov MV, Plyusnina EN, Zhavoronkov A, Budovsky A, Yanai H, et al. (2013). The role of DNA damage and repair in aging through the prism of Koch-like criteria. Aging Res Rev, 12: 661-684
http://dx.doi.org/10.1016/j.arr.2012.02.001
[4] Calabrese P, Shibata D (2010). A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates. BMC Cancer, 10: 1-12
http://118.145.16.217/magsci/article/article?id=15850837
[5] Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144: 646-674
http://118.145.16.217/magsci/article/article?id=21291497
[6] Negrini S, Gorgoulis VG, Halazonetis TD (2010). Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol, 11: 220-228
http://dx.doi.org/10.1038/nrm2858
[7] Roberts SA, Gordenin DA (2014). Hypermutation in human cancer genomes: footprints and mechanisms. Nature reviews. Cancer, 14: 786-800
[8] Steinke V, Engel C, Büttner R, Schackert HK, Schmiegel WH, Propping P (2013). Hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome. Dtsch Arztebl Int, 110: 32-38
http://118.145.16.217/magsci/article/article?id=19758126
[9] Roy R, Chun J, Powell SN (2012). BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer, 12: 68-78
[10] Half E, Bercovich D, Rozen P (2009). Familial adenomatous polyposis. Orphanet Journal of Rare Diseases, 4: 22
http://dx.doi.org/10.1186/1750-1172-4-22
[11] Bernstein KA, Gangloff S, Rothstein R (2010). The RecQ DNA helicases in DNA Repair. Annu Rev Genet, 44: 393-417
http://dx.doi.org/10.1146/annurev-genet-102209-163602
[12] Oshima J, Sidorova JM, Monnat RJJr., (2016). Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions. Aging Res Rev
[13] Kim S-Y, Hakoshima T, Kitano K (2013). Structure of the RecQ C-terminal domain of human Bloom syndrome protein. Scientific reports, 3
[14] Lauper JM, Krause A, Vaughan TL, Monnat RJJr (2013). Spectrum and risk of neoplasia in Werner syndrome: a systematic review. PloS one, 8: e59709
http://dx.doi.org/10.1371/journal.pone.0059709
[15] Cleaver JE (2005). Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nature Reviews Cancer, 5: 564-573
http://dx.doi.org/10.1038/nrc1652
[16] Zhang WR, Garrett GL, Cleaver JE, Arron ST Absence of skin cancer in the DNA repair-deficient disease Cockayne Syndrome (CS): A survey study. Journal of the American Academy of Dermatology, 74: 1270-1272
[17] Maslov AY, Vijg J (2009). Genome instability, cancer and aging. Biochim Biophys Acta, 1790: 963-969
http://dx.doi.org/10.1016/j.bbagen.2009.03.020
[18] Bahar R, Hartmann CH, Rodriguez KA, Denny AD, Busuttil RA, Dolle ME, et al. (2006). Increased cell-to-cell variation in gene expression in aging mouse heart. Nature, 441: 1011-1014
http://dx.doi.org/10.1038/nature04844
[19] Dollé MET, Snyder WK, Gossen JA, Lohman PHM, Vijg J (2000). Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine. Proceedings of the National Academy of Sciences of the United States of America, 97: 8403-8408
http://dx.doi.org/10.1073/pnas.97.15.8403
[20] Campisi J (2003). Cancer and aging: rival demons?. Nat Rev Cancer, 3: 339-349
http://dx.doi.org/10.1038/nrc1073
[21] Campisi J (2013). Aging, cellular senescence, and cancer. Annu Rev Physiol, 75: 685-705
http://118.145.16.217/magsci/article/article?id=20797625
[22] Tomasetti C, Vogelstein B (2015). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science, 347: 78-81
http://dx.doi.org/10.1126/science.1260825
[23] Olovnikov AM (1996). Telomeres, telomerase, and aging: origin of the theory. Exp Gerontol, 31: 443-448
http://dx.doi.org/10.1016/0531-5565(96)00005-8
[24] Bernardes de Jesus B, Blasco MA (2013). Telomerase at the intersection of cancer and aging. Trends in Genetics, 29: 513-520
http://118.145.16.217/magsci/article/article?id=20468989
[25] Shay JW, Wright WE (2000). Hayflick, his limit, and cellular aging. Nat Rev Mol Cell Biol, 1: 72-76
http://dx.doi.org/10.1038/35036093
[26] Hayflick L, Moorhead PS (1961). The serial cultivation of human diploid cell strains. Exp Cell Res, 25: 585-621
http://dx.doi.org/10.1016/0014-4827(61)90192-6
[27] Blackburn EH, Epel ES, Lin J (2015). Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science, 350: 1193-1198
http://dx.doi.org/10.1126/science.aab3389
[28] Walne AJ, Dokal I (2009). Advances in the understanding of dyskeratosis congenita. Br J Haematol, 145: 164-172
http://dx.doi.org/10.1111/j.1365-2141.2009.07598.x
[29] Cohen S, Janicki-Deverts D, Turner RB, Casselbrant ML, Li-Korotky HS, Epel ES, et al. (2013). Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults. Jama, 309: 699-705
http://dx.doi.org/10.1001/jama.2013.613
[30] Zhao J, Miao K, Wang H, Ding H, Wang DW (2013). Association between telomere length and type 2 diabetes mellitus: a meta-analysis. PLoS One, 8: e79993
http://dx.doi.org/10.1371/journal.pone.0079993
[31] Haycock PC, Heydon EE, Kaptoge S, Butterworth AS, Thompson A, Willeit P (2014). Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis. BMJ, 349
[32] Hunt SC, Kimura M, Hopkins PN, Carr JJ, Heiss G, Province MA, et al. (2015). Leukocyte Telomere Length and Coronary Artery Calcium. Am J Cardiol, 116: 214-218
http://dx.doi.org/10.1016/j.amjcard.2015.03.060
[33] Kuszel L, Trzeciak T, Richter M, Czarny-Ratajczak M (2015). Osteoarthritis and telomere shortening. J Appl Genet, 56: 169-176
http://dx.doi.org/10.1007/s13353-014-0251-8
[34] Carlquist JF, Knight S, Cawthon RM, Le VT, Bunch TJ, Horne BD, et al. (2015). Shortened Telomere Length is Associated with Paroxysmal Atrial Fibrillation Among Cardiovascular Patients Enrolled in the Intermountain Heart Collaborative Study. Heart Rhythm
[35] Forero DA, Gonzalez-Giraldo Y, Lopez-Quintero C, Castro-Vega LJ, Barreto GE, Perry G (2016). Meta-analysis of Telomere Length in Alzheimer’s Disease. J Gerontol A Biol Sci Med Sci, 71: 1069-1073
http://dx.doi.org/10.1093/gerona/glw053
[36] Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA (2003). Association between telomere length in blood and mortality in people aged 60 years or older. Lancet, 361: 393-395
http://dx.doi.org/10.1016/S0140-6736(03)12384-7
[37] Blasco MA (2007). Telomere length, stem cells and aging. Nat Chem Biol, 3: 640-649
http://dx.doi.org/10.1038/nchembio.2007.38
[38] Pereira B, Ferreira MG (2013). Sowing the seeds of cancer: telomeres and age-associated tumorigenesis. Curr Opin Oncol, 25: 93-98
http://118.145.16.217/magsci/article/article?id=19796609
[39] Honig LS, Kang MS, Cheng R, Eckfeldt JH, Thyagarajan B, Leiendecker-Foster C, et al. (2015). Heritability of telomere length in a study of long-lived families. Neurobiol Aging
[40] McGrath M, Wong JY, Michaud D, Hunter DJ, De Vivo I (2007). Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiol Biomarkers Prev, 16: 815-819
http://dx.doi.org/10.1158/1055-9965.EPI-06-0961
[41] Ma H, Zhou Z, Wei S, Liu Z, Pooley KA, Dunning AM, et al. (2011). Shortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis. PLoS ONE, 6: e20466
http://dx.doi.org/10.1371/journal.pone.0020466
[42] Willeit P, Willeit J, Kloss-Brandstatter A, Kronenberg F, Kiechl S (2011). Fifteen-year follow-up of association between telomere length and incident cancer and cancer mortality. JAMA, 306: 42-44
[43] Willeit P, Willeit J, Mayr A, Weger S, Oberhollenzer F, Brandstatter A, et al. (2010). Telomere length and risk of incident cancer and cancer mortality. Jama, 304: 69-75
http://dx.doi.org/10.1001/jama.2010.897
[44] Weischer M, Nordestgaard BG, Cawthon RM, Freiberg JJ, Tybjaerg-Hansen A, Bojesen SE (2013). Short telomere length, cancer survival, and cancer risk in 47102 individuals. J Natl Cancer Inst, 105: 459-468
http://dx.doi.org/10.1093/jnci/djt016
[45] Zhang C, Chen X, Li L, Zhou Y, Wang C, Hou S (2015). The Association between Telomere Length and Cancer Prognosis: Evidence from a Meta-Analysis. PLoS ONE, 10: e0133174
http://dx.doi.org/10.1371/journal.pone.0133174
[46] Rode L, Nordestgaard BG, Bojesen SE (2015). Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population. J Natl Cancer Inst, 107: djv074
[47] Wentzensen IM, Mirabello L, Pfeiffer RM, Savage SA (2011). The association of telomere length and cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev, 20: 1238-1250
http://dx.doi.org/10.1158/1055-9965.EPI-11-0005
[48] Hou L, Joyce BT, Gao T, Liu L, Zheng Y, Penedo FJ, et al. (2015). Blood Telomere Length Attrition and Cancer Development in the Normative Aging Study Cohort. EBioMedicine, 2: 591-596
http://dx.doi.org/10.1016/j.ebiom.2015.04.008
[49] Aunan JR, Watson MM, Hagland HR, Soreide K (2016). Molecular and biological hallmarks of aging. Br J Surg, 103: e29-46
http://dx.doi.org/10.1002/bjs.10053
[50] Maegawa S, Hinkal G, Kim HS, Shen L, Zhang L, Zhang J, et al. (2010). Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res, 20: 332-340
http://dx.doi.org/10.1101/gr.096826.109
[51] Osorio FG, Varela I, Lara E, Puente XS, Espada J, Santoro R, et al. (2010). Nuclear envelope alterations generate an aging-like epigenetic pattern in mice deficient in Zmpste24 metalloprotease. Aging Cell, 9: 947-957
http://dx.doi.org/10.1111/j.1474-9726.2010.00621.x
[52] Chen BH, Marioni RE, Colicino E, Peters MJ, Ward-Caviness CK, Tsai PC, et al. (2016). DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging (Albany NY), 8: 1844-1865
[53] Horvath S (2013). DNA methylation age of human tissues and cell types. Genome Biol, 14: R115
http://dx.doi.org/10.1186/gb-2013-14-10-r115
[54] Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, et al. (2013). Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell, 49: 359-367
http://dx.doi.org/10.1016/j.molcel.2012.10.016
[55] Daniel M, Tollefsbol TO (2015). Epigenetic linkage of aging, cancer and nutrition. J Exp Biol, 218: 59-70
http://dx.doi.org/10.1242/jeb.107110
[56] Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, et al. (2003). Induction of tumors in mice by genomic hypomethylation. Science, 300: 489-492
http://dx.doi.org/10.1126/science.1083558
[57] Hur K, Cejas P, Feliu J, Moreno-Rubio J, Burgos E, Boland CR, et al. (2014). Hypomethylation of long interspersed nuclear element-1 (LINE-1) leads to activation of proto-oncogenes in human colorectal cancer metastasis. Gut, 63: 635-646
http://118.145.16.217/magsci/article/article?id=22850041
[58] Soes S, Daugaard IL, Sorensen B, Carus A, Mattheisen M, Alsner J, et al. (2014). Hypomethylation and increased expression of the putative oncogene ELMO3 are associated with lung cancer development and metastases formation. Oncoscience, 1: 367-374
http://dx.doi.org/10.18632/oncoscience.42
[59] Wang Y, Li Y, Liu X, Cho WC (2013). Genetic and epigenetic studies for determining molecular targets of natural product anticancer agents. Curr Cancer Drug Targets, 13: 506-518
http://dx.doi.org/10.2174/15680096113139990033
[60] Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, et al. (2016). Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature, 534: 47-54
http://dx.doi.org/10.1038/nature17676
[61] Michalak EM, Visvader JE Dysregulation of histone methyltransferases in breast cancer – Opportunities for new targeted therapies?. Molecular Oncology
[62] Maleszewska M, Mawer JSP, Tessarz P (2016). Histone Modifications in Aging and Lifespan Regulation. Current Molecular Biology Reports, 2: 26-35
http://dx.doi.org/10.1007/s40610-016-0031-9
[63] Lu J, Clark AG (2012). Impact of microRNA regulation on variation in human gene expression. Genome Res, 22: 1243-1254
http://dx.doi.org/10.1101/gr.132514.111
[64] Zhao Y, Deng C, Wang J, Xiao J, Gatalica Z, Recker RR, et al. (2011). Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer. Breast Cancer Res Treat, 127: 69-80
http://dx.doi.org/10.1007/s10549-010-0972-2
[65] Dellago H, Bobbili MR, Grillari J (2016). MicroRNA-17-5p: At the Crossroads of Cancer and Aging - A Mini-Review. Gerontology
[66] Yu HW, Cho WC (2015). The emerging role of miRNAs in combined cancer therapy. Expert Opinion on Biological Therapy, 15: 923-925
http://dx.doi.org/10.1517/14712598.2015.1030390
[67] Maiese K (2016). Disease onset and aging in the world of circular RNAs. Journal of translational science, 2: 327-329
[68] Qu S, Zhong Y, Shang R, Zhang X, Song W, Kjems J, et al. (2016). The emerging landscape of circular RNA in life processes. RNA Biology: 1-8
[69] Labbadia J, Morimoto RI (2015). The biology of proteostasis in aging and disease. Annu Rev Biochem, 84: 435-464
http://dx.doi.org/10.1146/annurev-biochem-060614-033955
[70] Clark AR, Lubsen NH, Slingsby C (2012). sHSP in the eye lens: crystallin mutations, cataract and proteostasis. Int J Biochem Cell Biol, 44: 1687-1697
http://dx.doi.org/10.1016/j.biocel.2012.02.015
[71] Koga H, Kaushik S, Cuervo AM (2011). Protein homeostasis and aging: The importance of exquisite quality control. Aging Res Rev, 10: 205-215
http://118.145.16.217/magsci/article/article?id=14835946
[72] Rappa F, Farina F, Zummo G, David S, Campanella C, Carini F, et al. (2012). HSP-molecular chaperones in cancer biogenesis and tumor therapy: an overview. Anticancer Res, 32: 5139-5150
http://118.145.16.217/magsci/article/article?id=24216320
[73] Calderwood SK, Murshid A, Prince T (2009). The shock of aging: molecular chaperones and the heat shock response in longevity and aging--a mini-review. Gerontology, 55: 550-558
http://dx.doi.org/10.1159/000225957
[74] Murshid A, Eguchi T, Calderwood SK (2013). Stress Proteins in Aging and Life Span. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 29: 442-447
http://dx.doi.org/10.3109/02656736.2013.798873
[75] Cuervo AM, Wong E (2014). Chaperone-mediated autophagy: roles in disease and aging. Cell Res, 24: 92-104
http://118.145.16.217/magsci/article/article?id=22618884
[76] Macario AJ, Cappello F, Zummo G, Conway de Macario E (2010). Chaperonopathies of senescence and the scrambling of interactions between the chaperoning and the immune systems. Ann N Y Acad Sci, 1197: 85-93
http://dx.doi.org/10.1111/j.1749-6632.2010.05187.x
[77] Pearl LH, Prodromou C, Workman P (2008). The Hsp90 molecular chaperone: an open and shut case for treatment. Biochem J, 410: 439-453
http://dx.doi.org/10.1042/BJ20071640
[78] Dai C, Sampson SB (2016). HSF1: Guardian of Proteostasis in Cancer. Trends in Cell Biology, 26: 17-28
http://dx.doi.org/10.1016/j.tcb.2015.10.011
[79] Joly AL, Wettstein G, Mignot G, Ghiringhelli F, Garrido C (2010). Dual role of heat shock proteins as regulators of apoptosis and innate immunity. J Innate Immun, 2: 238-247
http://dx.doi.org/10.1159/000296508
[80] Garcia-Carbonero R, Carnero A, Paz-Ares L (2013). Inhibition of HSP90 molecular chaperones: moving into the clinic. The Lancet Oncology, 14: e358-e369
http://dx.doi.org/10.1016/S1470-2045(13)70169-4
[81] Chettiar ST, Malek R, Annadanam A, Nugent KM, Kato Y, Wang H, et al. (2016). Ganetespib radiosensitization for liver cancer therapy. Cancer Biol Ther, 17: 457-466
http://dx.doi.org/10.1080/15384047.2016.1156258
[82] Bailey CK, Budina-Kolomets A, Murphy ME, Nefedova Y (2015). Efficacy of the HSP70 inhibitor PET-16 in multiple myeloma. Cancer Biol Ther, 16: 1422-1426
http://dx.doi.org/10.1080/15384047.2015.1071743
[83] Chi KN, Yu EY, Jacobs C, Bazov J, Kollmannsberger C, Higano CS, et al. (2016). A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castration-resistant prostate cancer and other advanced cancers. Ann Oncol, 27: 1116-1122
http://dx.doi.org/10.1093/annonc/mdw068
[84] Chondrogianni N, Sakellari M, Lefaki M, Papaevgeniou N, Gonos ES (2014). Proteasome activation delays aging in vitro and in vivo. Free Radic Biol Med, 71: 303-320
http://dx.doi.org/10.1016/j.freeradbiomed.2014.03.031
[85] Chondrogianni N, Petropoulos I, Franceschi C, Friguet B, Gonos ES (2000). Fibroblast cultures from healthy centenarians have an active proteasome. Exp Gerontol, 35: 721-728
http://dx.doi.org/10.1016/S0531-5565(00)00137-6
[86] Dou QP, Zonder JA (2014). Overview of Proteasome Inhibitor-Based Anti-cancer Therapies: Perspective on Bortezomib and Second Generation Proteasome Inhibitors versus Future Generation Inhibitors of Ubiquitin-Proteasome System. Current cancer drug targets, 14: 517-536
http://118.145.16.217/magsci/article/article?id=22683377
[87] Mizushima N, Komatsu M (2011). Autophagy: renovation of cells and tissues. Cell, 147: 728-741
http://118.145.16.217/magsci/article/article?id=21303704
[88] Anton S, Leeuwenburgh C (2013). Fasting or caloric restriction for Healthy Aging.
[89] Weindruch R (1996). The retardation of aging by caloric restriction: studies in rodents and primates. Toxicol Pathol, 24: 742-745
http://dx.doi.org/10.1177/019262339602400618
[90] Chung KW, Kim DH, Park MH, Choi YJ, Kim ND, Lee J, et al. (2013). Recent advances in calorie restriction research on aging. Exp Gerontol, 48: 1049-1053
http://118.145.16.217/magsci/article/article?id=19821653
[91] Hursting SD, Dunlap SM, Ford NA, Hursting MJ, Lashinger LM (2013). Calorie restriction and cancer prevention: a mechanistic perspective. Cancer & Metabolism, 1: 10
http://dx.doi.org/10.1186/2049-3002-1-10
[92] Rubinsztein DC, Marino G, Kroemer G (2011). Autophagy and aging. Cell, 146: 682-695
http://118.145.16.217/magsci/article/article?id=21275031
[93] Madeo F, Zimmermann A, Maiuri MC, Kroemer G (2015). Essential role for autophagy in life span extension. J Clin Invest, 125: 85-93
http://dx.doi.org/10.1172/JCI73946
[94] Catalgol B, Batirel S, Taga Y, Ozer NK (2012). Resveratrol: French paradox revisited. Front Pharmacol, 3: 141
[95] Thorburn A, Thamm DH, Gustafson DL (2014). Autophagy and Cancer Therapy. Molecular Pharmacology, 85: 830-838
http://118.145.16.217/magsci/article/article?id=23411130
[96] White E The role for autophagy in cancer. The Journal of Clinical Investigation, 125: 42-46
http://dx.doi.org/10.1172/JCI73941
[97] Djiogue S, Nwabo Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y, et al. (2013). Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer, 20: R1-r17
http://118.145.16.217/magsci/article/article?id=19810142
[98] Fontana L, Partridge L, Longo VD (2010). Extending healthy life span--from yeast to humans. Science, 328: 321-326
http://dx.doi.org/10.1126/science.1172539
[99] Jenkins PJ, Mukherjee A, Shalet SM (2006). Does growth hormone cause cancer?. Clin Endocrinol (Oxf), 64: 115-121
http://dx.doi.org/10.1111/j.1365-2265.2005.02404.x
[100] Duggan C, Wang CY, Neuhouser ML, Xiao L, Smith AW, Reding KW, et al. (2013). Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer. Int J Cancer, 132: 1191-1200
http://dx.doi.org/10.1002/ijc.27753
[101] Li D (2012). Diabetes and pancreatic cancer. Mol Carcinog, 51: 64-74
http://dx.doi.org/10.1002/mc.20771
[102] Mu N, Zhu Y, Wang Y, Zhang H, Xue F (2012). Insulin resistance: a significant risk factor of endometrial cancer. Gynecol Oncol, 125: 751-757
http://118.145.16.217/magsci/article/article?id=23903246
[103] Byers T, Sedjo RL (2011). Does intentional weight loss reduce cancer risk?. Diabetes Obes Metab, 13: 1063-1072
http://118.145.16.217/magsci/article/article?id=21396910
[104] Pollak M (2012). The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer, 12: 159-169
[105] Zaytseva YY, Valentino JD, Gulhati P, Evers BM (2012). mTOR inhibitors in cancer therapy. Cancer Lett, 319: 1-7
http://118.145.16.217/magsci/article/article?id=24387684
[106] Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumors of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. The Lancet, 387: 968-977
http://dx.doi.org/10.1016/S0140-6736(15)00817-X
[107] Rehman G, Shehzad A, Khan AL, Hamayun M (2014). Role of AMP-activated protein kinase in cancer therapy. Arch Pharm (Weinheim), 347: 457-468
http://dx.doi.org/10.1002/ardp.201300402
[108] Blagosklonny MV (2013). Selective anti-cancer agents as anti-aging drugs. Cancer Biol Ther, 14: 1092-1097
http://dx.doi.org/10.4161/cbt.27350
[109] Finkel T, Serrano M, Blasco MA (2007). The common biology of cancer and aging. Nature, 448: 767-774
http://dx.doi.org/10.1038/nature05985
[110] Collado M, Serrano M (2010). Senescence in tumors: evidence from mice and humans. Nature reviews. Cancer, 10: 51-57
[111] Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL (2013). Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest, 123: 966-972
http://118.145.16.217/magsci/article/article?id=20042859
[112] Falandry C, Bonnefoy M, Freyer G, Gilson E (2014). Biology of Cancer and Aging: A Complex Association With Cellular Senescence. Journal of Clinical Oncology
http://118.145.16.217/magsci/article/article?id=23122276
[113] Coppé J-P, Desprez P-Y, Krtolica A, Campisi J (2010). The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression. Annual review of pathology, 5: 99-118
http://dx.doi.org/10.1146/annurev-pathol-121808-102144
[114] Cho WC, Kwan CK, Yau S, So PP, Poon PC, Au JS (2011). The role of inflammation in the pathogenesis of lung cancer. Expert Opin Ther Targets, 15: 1127-1137
http://dx.doi.org/10.1517/14728222.2011.599801
[115] Wei J, Li F, Yang J, Liu X, Cho WC (2015). MicroRNAs as regulators of airborne pollution-induced lung inflammation and carcinogenesis. Arch Toxicol, 89: 677-685
http://dx.doi.org/10.1007/s00204-015-1462-4
[116] LaPak KM, Burd CE (2014). The molecular balancing act of p16(INK4a) in cancer and aging. Mol Cancer Res, 12: 167-183
http://118.145.16.217/magsci/article/article?id=23417728
[117] Jeck WR, Siebold AP, Sharpless NE (2012). Review: a meta-analysis of GWAS and age-associated diseases. Aging Cell, 11: 727-731
http://dx.doi.org/10.1111/j.1474-9726.2012.00871.x
[118] Boquoi A, Arora S, Chen T, Litwin S, Koh J, Enders GH (2015). Reversible cell cycle inhibition and premature aging features imposed by conditional expression of p16Ink4a. Aging Cell, 14: 139-147
http://dx.doi.org/10.1111/acel.12279
[119] Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, et al. (2011). Clearance of p16Ink4a-positive senescent cells delays aging-associated disorders. Nature, 479: 232-236
http://dx.doi.org/10.1038/nature10600
[120] Geiger H, de Haan G, Florian MC (2013). The aging haematopoietic stem cell compartment. Nat Rev Immunol, 13: 376-389
http://dx.doi.org/10.1038/nri3433
[121] Noronha-Matos JB, Correia-de-Sa P (2016). Mesenchymal Stem Cells Aging: Targeting the "Purinome" to Promote Osteogenic Differentiation and Bone Repair. J Cell Physiol, 231: 1852-1861
http://dx.doi.org/10.1002/jcp.25303
[122] Sousa-Victor P, Munoz-Canoves P (2016). Regenerative decline of stem cells in sarcopenia. Mol Aspects Med, 50: 109-117
http://dx.doi.org/10.1016/j.mam.2016.02.002
[123] Rossi DJ, Jamieson CH, Weissman IL (2008). Stems cells and the pathways to aging and cancer. Cell, 132: 681-696
http://dx.doi.org/10.1016/j.cell.2008.01.036
[124] Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL (2007). Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature, 447: 725-729
http://dx.doi.org/10.1038/nature05862
[1] Adar Zinger,William C Cho,Arie Ben-Yehuda. Cancer and Aging - the Inflammatory Connection[J]. A&D, 2017, 8(5): 611-627.
[2] Ulises Urzua,Carlos Chacon,Luis Lizama,Sebastián Sarmiento,Pía Villalobos,Belén Kroxato,Katherine Marcelain,María-Julieta Gonzalez. Parity History Determines a Systemic Inflammatory Response to Spread of Ovarian Cancer in Naturally Aged Mice[J]. A&D, 2017, 8(5): 546-557.
[3] Ilia Stambler. Recognizing Degenerative Aging as a Treatable Medical Condition: Methodology and Policy[J]. A&D, 2017, 8(5): 583-589.
[4] Liang Yan,Rui Gao,Yang Liu,Baorong He,Shemin Lv,Dingjun Hao. The Pathogenesis of Ossification of the Posterior Longitudinal Ligament[J]. A&D, 2017, 8(5): 570-582.
[5] Xianglai Xu,Brian Wang,Changhong Ren,Jiangnan Hu,David A. Greenberg,Tianxiang Chen,Liping Xie,Kunlin Jin. Age-related Impairment of Vascular Structure and Functions[J]. A&D, 2017, 8(5): 590-610.
[6] Mariaelena Occhipinti,Anna Rita Larici,Lorenzo Bonomo,Raffaele Antonelli Incalzi. Aging Airways: between Normal and Disease. A Multidimensional Diagnostic Approach by Combining Clinical, Functional, and Imaging Data[J]. A&D, 2017, 8(4): 471-485.
[7] Marta K. Zamroziewicz,Erick J. Paul,Chris E. Zwilling,Aron K. Barbey. Predictors of Memory in Healthy Aging: Polyunsaturated Fatty Acid Balance and Fornix White Matter Integrity[J]. A&D, 2017, 8(4): 372-383.
[8] Xianglai Xu,Brian Wang,Changhong Ren,Jiangnan Hu,David A. Greenberg,Tianxiang Chen,Liping Xie,Kunlin Jin. Recent Progress in Vascular Aging: Mechanisms and Its Role in Age-related Diseases[J]. A&D, 2017, 8(4): 486-505.
[9] Alexey Moskalev,Elizaveta Chernyagina,Anna Kudryavtseva,Mikhail Shaposhnikov. Geroprotectors: A Unified Concept and Screening Approaches[J]. A&D, 2017, 8(3): 354-363.
[10] Alan R. Hipkiss. On the Relationship between Energy Metabolism, Proteostasis, Aging and Parkinson’s Disease: Possible Causative Role of Methylglyoxal and Alleviative Potential of Carnosine[J]. A&D, 2017, 8(3): 334-345.
[11] Minwen Xu,Olga Sizova,Liefeng Wang,Dong-Ming Su. A Fine-Tune Role of Mir-125a-5p on Foxn1 During Age-Associated Changes in the Thymus[J]. A&D, 2017, 8(3): 277-286.
[12] Qianfa Long,Qiang Luo,Kai Wang,Adrian Bates,Ashok K. Shetty. Mash1-dependent Notch Signaling Pathway Regulates GABAergic Neuron-Like Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells[J]. A&D, 2017, 8(3): 301-313.
[13] Guangxian Zhao,Xian W. Cheng,Limei Piao,Lina Hu,Yanna Lei,Guang Yang,Aiko Inoue,Shinyu Ogasawara,Hongxian Wu,Chang-Ning Hao,Kenji Okumura,Masafumi Kuzuya. The Soluble VEGF Receptor sFlt-1 Contributes to Impaired Neovascularization in Aged Mice[J]. A&D, 2017, 8(3): 287-300.
[14] Massimo De Martinis,Maria Maddalena Sirufo,Lia Ginaldi. Allergy and Aging: An Old/New Emerging Health Issue[J]. A&D, 2017, 8(2): 162-175.
[15] Hongxia Zhang,Fen Sun,Jixian Wang,Luokun Xie,Chenqi Yang,Mengxiong Pan,Bei Shao,Guo-Yuan Yang,Shao-Hua Yang,Qichuan ZhuGe,Kunlin Jin. Combining Injectable Plasma Scaffold with Mesenchymal Stem/Stromal Cells for Repairing Infarct Cavity after Ischemic Stroke[J]. A&D, 2017, 8(2): 203-214.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd