Skip to main content

Advertisement

Log in

Effects of aging on apoptosis gene expression in oral mucosal tissues

  • Original Paper
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = 23) were used in a cross-sectional study to obtain clinical healthy gingival tissues specimens. Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated. The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes. The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca+2-induced death signaling, cell cycle checkpoints, and potential effects of survival factors. Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals. The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Stower H (2012) Microbiology: the human microbiome project. Nat Rev Genet 13:518

    PubMed  CAS  Google Scholar 

  2. Torchinsky MB, Garaude J, Blander JM (2010) Infection and apoptosis as a combined inflammatory trigger. Curr Opin Immunol 22:55–62

    Article  PubMed  CAS  Google Scholar 

  3. Kuranaga E (2011) Caspase signaling in animal development. Dev Growth Differ 53:137–148

    Article  PubMed  CAS  Google Scholar 

  4. Yuan J, Kroemer G (2010) Alternative cell death mechanisms in development and beyond. Genes Dev 24:2592–2602

    Article  PubMed  CAS  Google Scholar 

  5. Ryoo HD, Bergmann A (2012) The role of apoptosis-induced proliferation for regeneration and cancer. Cold Spring Harb Perspect Biol 4(8):a008797. doi:10.1101/cshperspect.a008797

    Article  PubMed  Google Scholar 

  6. Cario E (2008) Innate immune signalling at intestinal mucosal surfaces: a fine line between host protection and destruction. Curr Opin Gastroenterol 24:725–732

    Article  PubMed  CAS  Google Scholar 

  7. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898

    Article  PubMed  CAS  Google Scholar 

  8. Kim S, Elkon KB, Ma X (2004) Transcriptional suppression of interleukin-12 gene expression following phagocytosis of apoptotic cells. Immunity 21:643–653

    Article  PubMed  CAS  Google Scholar 

  9. Paster BJ, Olsen I, Aas JA, Dewhirst FE (2006) The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontol 2000 42:80–87

    Article  PubMed  Google Scholar 

  10. Colombo AP, Boches SK, Cotton SL, Goodson JM, Kent R, Haffajee AD, Socransky SS, Hasturk H, Van Dyke TE, Dewhirst F, Paster BJ (2009) Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray. J Periodontol 80:1421–1432

    Article  PubMed  CAS  Google Scholar 

  11. Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE (2005) Defining the normal bacterial flora of the oral cavity. J Clin Microbiol 43:5721–5732

    Article  PubMed  Google Scholar 

  12. Kolenbrander PE (2011) Multispecies communities: interspecies interactions influence growth on saliva as sole nutritional source. Int J Oral Sci 3:49–54

    Article  PubMed  Google Scholar 

  13. Periasamy S, Kolenbrander PE (2009) Mutualistic biofilm communities develop with Porphyromonas gingivalis and initial, early, and late colonizers of enamel. J Bacteriol 191:6804–6811

    Article  PubMed  CAS  Google Scholar 

  14. Gonzalez OA, Stromberg AJ, Huggins PM, Gonzalez-Martinez J, Novak MJ, Ebersole JL (2011) Apoptotic genes are differentially expressed in aged gingival tissue. J Dent Res 90:880–886

    Article  PubMed  CAS  Google Scholar 

  15. Willershausen-Zonnchen B, Gleissner C (1998) Periodontal disease in elderly patients. Eur J Med Res 3:55–64

    PubMed  CAS  Google Scholar 

  16. Garcia RI, Krall EA, Vokonas PS (1998) Periodontal disease and mortality from all causes in the VA Dental Longitudinal Study. Ann Periodontol 3:339–349

    Article  PubMed  CAS  Google Scholar 

  17. Ship JA, Crow HC (1994) Diseases of periodontal tissues in the elderly. Description, epidemiology, aetiology and drug therapy. Drugs Aging 5:346–357

    Article  PubMed  CAS  Google Scholar 

  18. Ebersole JL, Steffen MJ, Gonzalez-Martinez J, Novak MJ (2008) Effects of age and oral disease on systemic inflammatory and immune parameters in nonhuman primates. Clin Vaccine Immunol 15:1067–1075

    Article  PubMed  CAS  Google Scholar 

  19. Meka A, Bakthavatchalu V, Sathishkumar S, Lopez MC, Verma RK, Wallet SM, Bhattacharyya I, Boyce BF, Handfield M, Lamont RJ, Baker HV, Ebersole JL, Kesavalu L (2010) Porphyromonas gingivalis infection-induced tissue and bone transcriptional profiles. Mol Oral Microbiol 25:61–74

    Article  PubMed  CAS  Google Scholar 

  20. Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V (2012) Role of apoptosis in disease. Aging 4:330–349

    PubMed  CAS  Google Scholar 

  21. Vaux DL, Korsmeyer SJ (1999) Cell death in development. Cell 96:245–254

    Article  PubMed  CAS  Google Scholar 

  22. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I (1997) Immunosuppressive effects of apoptotic cells. Nature 390:350–351

    Article  PubMed  CAS  Google Scholar 

  23. Gamonal J, Bascones A, Acevedo A, Blanco E, Silva A (2001) Apoptosis in chronic adult periodontitis analyzed by in situ DNA breaks, electron microscopy, and immunohistochemistry. J Periodontol 72:517–525

    Article  PubMed  CAS  Google Scholar 

  24. Koulouri O, Lappin DF, Radvar M, Kinane DF (1999) Cell division, synthetic capacity and apoptosis in periodontal lesions analysed by in situ hybridisation and immunohistochemistry. J Clin Periodontol 26:552–559

    Article  PubMed  CAS  Google Scholar 

  25. Albandar JM, Tinoco EM (2002) Global epidemiology of periodontal diseases in children and young persons. Periodontol 2000 29:153–176

    Article  PubMed  Google Scholar 

  26. Streckfus CF, Parsell DE, Streckfus JE, Pennington W, Johnson RB (1999) Relationship between oral alveolar bone loss and aging among African-American and Caucasian individuals. Gerontology 45:110–114

    Article  PubMed  CAS  Google Scholar 

  27. Rider P, Carmi Y, Guttman O, Braiman A, Cohen I, Voronov E, White MR, Dinarello CA, Apte RN (2011) IL-1alpha and IL-1beta recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol 187:4835–4843

    Article  PubMed  CAS  Google Scholar 

  28. Berda-Haddad Y, Robert S, Salers P, Zekraoui L, Farnarier C, Dinarello CA, Dignat-George F, Kaplanski G (2011) Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by interleukin-1α. Proc Natl Acad Sci USA 108:20684–20689

    Article  PubMed  CAS  Google Scholar 

  29. Cohen-Sfady M, Pevsner-Fischer M, Margalit R, Cohen IR (2009) Heat shock protein 60, via MyD88 innate signaling, protects B cells from apoptosis, spontaneous and induced. J Immunol 183:890–896

    Article  PubMed  CAS  Google Scholar 

  30. Busca A, Saxena M, Kryworuchko M, Kumar A (2009) Anti-apoptotic genes in the survival of monocytic cells during infection. Curr Genomics 10:306–317

    Article  PubMed  CAS  Google Scholar 

  31. Schmid JA, Birbach A (2008) IkappaB kinase beta (IKKbeta/IKK2/IKBKB)—a key molecule in signaling to the transcription factor NF-kappaB. Cytokine Growth Factor Rev 19:157–165

    Article  PubMed  CAS  Google Scholar 

  32. Sethi G, Ahn KS, Aggarwal BB (2008) Targeting nuclear factor-kappa B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res 6:1059–1070

    Article  PubMed  CAS  Google Scholar 

  33. Reubold TF, Eschenburg S (2012) A molecular view on signal transduction by the apoptosome. Cell Signal 24:1420–1425

    Article  PubMed  CAS  Google Scholar 

  34. Lawrence T, Fong C (2010) The resolution of inflammation: anti-inflammatory roles for NF-kappaB. Int J Biochem Cell Biol 42:519–523

    Article  PubMed  CAS  Google Scholar 

  35. Brown KD, Claudio E, Siebenlist U (2008) The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis. Arthr Res Ther 10:212

    Article  Google Scholar 

  36. Vogler M (2012) BCL2A1: the underdog in the BCL2 family. Cell Death Differ 19:67–74

    Article  PubMed  CAS  Google Scholar 

  37. Zhou F, Yang Y, Xing D (2011) Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis. FEBS J 278:403–413

    Article  PubMed  CAS  Google Scholar 

  38. Kumar S (1995) ICE-like proteases in apoptosis. Trends Biochem Sci 20:198–202

    Article  PubMed  CAS  Google Scholar 

  39. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA et al (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43

    Article  PubMed  CAS  Google Scholar 

  40. Wallach D, Boldin M, Goncharov T, Goltsev Y, Mett I, Malinin N, Adar R, Kovalenko A, Varfolomeev E (1996) Exploring cell death mechanisms by analyzing signaling cascades of the TNF/NGF receptor family. Behring Inst Mitt (97):144–155

  41. Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death–inducing signaling complex. Cell 85:817–827

    Article  PubMed  CAS  Google Scholar 

  42. Rosen A, Casciola-Rosen L (1997) Macromolecular substrates for the ICE-like proteases during apoptosis. J Cell Biochem 64:50–54

    Article  PubMed  CAS  Google Scholar 

  43. Sabatel H, Pirlot C, Piette J, Habraken Y (2011) Importance of PIKKs in NF-kappaB activation by genotoxic stress. Biochem Pharmacol 82:1371–1383

    Article  PubMed  CAS  Google Scholar 

  44. Bononi A, Agnoletto C, De Marchi E, Marchi S, Patergnani S, Bonora M, Giorgi C, Missiroli S, Poletti F, Rimessi A, Pinton P (2011) Protein kinases and phosphatases in the control of cell fate. Enzyme Res 2011:329098

    Article  PubMed  Google Scholar 

  45. Duronio V (2008) The life of a cell: apoptosis regulation by the PI3K/PKB pathway. Biochem J 415:333–344

    Article  PubMed  CAS  Google Scholar 

  46. Insel PA, Zhang L, Murray F, Yokouchi H, Zambon AC (2012) Cyclic AMP is both a pro-apoptotic and anti-apoptotic second messenger. Acta Physiol (Oxf) 204:277–287

    Article  CAS  Google Scholar 

  47. Yonezawa T, Kurata R, Kimura M, Inoko H (2011) Which CIDE are you on? Apoptosis and energy metabolism. Mol BioSyst 7:91–100

    Article  PubMed  CAS  Google Scholar 

  48. Kfir-Erenfeld S, Sionov RV, Spokoini R, Cohen O, Yefenof E (2010) Protein kinase networks regulating glucocorticoid-induced apoptosis of hematopoietic cancer cells: fundamental aspects and practical considerations. Leuk Lymphoma 51:1968–2005

    Article  PubMed  CAS  Google Scholar 

  49. Taylor SS, Kim C, Vigil D, Haste NM, Yang J, Wu J, Anand GS (2005) Dynamics of signaling by PKA. Biochim Biophys Acta 1754:25–37

    Article  PubMed  CAS  Google Scholar 

  50. Taylor SS, Yang J, Wu J, Haste NM, Radzio-Andzelm E, Anand G (2004) PKA: a portrait of protein kinase dynamics. Biochim Biophys Acta 1697:259–269

    Article  PubMed  CAS  Google Scholar 

  51. Bossis I, Voutetakis A, Bei T, Sandrini F, Griffin KJ, Stratakis CA (2004) Protein kinase A and its role in human neoplasia: the Carney complex paradigm. Endocr Relat Cancer 11:265–280

    Article  PubMed  CAS  Google Scholar 

  52. Cho-Chung YS, Nesterova M, Becker KG, Srivastava R, Park YG, Lee YN, Cho YS, Kim MK, Neary C, Cheadle C (2002) Dissecting the circuitry of protein kinase A and cAMP signaling in cancer genesis: antisense, microarray, gene overexpression, and transcription factor decoy. Ann N Y Acad Sci 968:22–36

    Article  PubMed  CAS  Google Scholar 

  53. Mair W, Morantte I, Rodrigues AP, Manning G, Montminy M, Shaw RJ, Dillin A (2011) Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470:404–408

    Article  PubMed  CAS  Google Scholar 

  54. Cypess AM, Zhang H, Schulz TJ, Huang TL, Espinoza DO, Kristiansen K, Unterman TG, Tseng YH (2011) Insulin/IGF-I regulation of necdin and brown adipocyte differentiation via CREB- and FoxO1-associated pathways. Endocrinology 152:3680–3689

    Article  PubMed  CAS  Google Scholar 

  55. Fernandes ND, Sun Y, Price BD (2007) Activation of the kinase activity of ATM by retinoic acid is required for CREB-dependent differentiation of neuroblastoma cells. J Biol Chem 282:16577–16584

    Article  PubMed  CAS  Google Scholar 

  56. Chowdhury I, Tharakan B, Bhat GK (2008) Caspases—an update. Comp Biochem Physiol B Biochem Mol Biol 151:10–27

    Article  PubMed  Google Scholar 

  57. Valmiki MG, Ramos JW (2009) Death effector domain-containing proteins. Cell Mol Life Sci 66:814–830

    Article  PubMed  CAS  Google Scholar 

  58. Sheikh MS, Huang Y (2003) Death receptor activation complexes: it takes two to activate TNF receptor 1. Cell Cycle 2:550–552

    PubMed  CAS  Google Scholar 

  59. Takahashi K, Kawai T, Kumar H, Sato S, Yonehara S, Akira S (2006) Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA. J Immunol 176:4520–4524

    PubMed  CAS  Google Scholar 

  60. Kulikov AV, Shilov ES, Mufazalov IA, Gogvadze V, Nedospasov SA, Zhivotovsky B (2012) Cytochrome c: the Achilles’ heel in apoptosis. Cell Mol Life Sci 69:1787–1797

    Article  PubMed  CAS  Google Scholar 

  61. Mates JM, Segura JA, Alonso FJ, Marquez J (2012) Oxidative stress in apoptosis and cancer: an update. Arch Toxicol 86(11):1649–1665

    Article  PubMed  CAS  Google Scholar 

  62. Smolewski P, Robak T (2011) Inhibitors of apoptosis proteins (IAPs) as potential molecular targets for therapy of hematological malignancies. Curr Mol Med 11:633–649

    Article  PubMed  CAS  Google Scholar 

  63. Gyrd-Hansen M, Meier P (2010) IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer 10:561–574

    Article  PubMed  CAS  Google Scholar 

  64. Widlak P, Garrard WT (2005) Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G. J Cell Biochem 94:1078–1087

    Article  PubMed  CAS  Google Scholar 

  65. Widlak P, Garrard WT (2009) Roles of the major apoptotic nuclease-DNA fragmentation factor-in biology and disease. Cell Mol Life Sci 66:263–274

    Article  PubMed  CAS  Google Scholar 

  66. Zhang JH, Xu M (2000) DNA fragmentation in apoptosis. Cell Res 10:205–211

    Article  PubMed  CAS  Google Scholar 

  67. Lavrik IN, Krammer PH (2012) Regulation of CD95/Fas signaling at the DISC. Cell Death Differ 19:36–41

    Article  PubMed  CAS  Google Scholar 

  68. Kurji K, Sharma RK (2010) Potential role of calcineurin in pathogenic conditions. Mol Cell Biochem 338:133–141

    Article  PubMed  CAS  Google Scholar 

  69. Manicassamy S, Gupta S, Huang Z, Molkentin JD, Shang W, Sun Z (2008) Requirement of calcineurin a beta for the survival of naive T cells. J Immunol 180:106–112

    PubMed  CAS  Google Scholar 

  70. Srinivasan M, Frauwirth KA (2007) Reciprocal NFAT1 and NFAT2 nuclear localization in CD8+ anergic T cells is regulated by suboptimal calcium signaling. J Immunol 179:3734–3741

    PubMed  CAS  Google Scholar 

  71. Sieber M, Karanik M, Brandt C, Blex C, Podtschaske M, Erdmann F, Rost R, Serfling E, Liebscher J, Patzel M, Radbruch A, Fischer G, Baumgrass R (2007) Inhibition of calcineurin–NFAT signaling by the pyrazolopyrimidine compound NCI3. Eur J Immunol 37:2617–2626

    Article  PubMed  CAS  Google Scholar 

  72. Morio T, Kim H (2008) Ku, Artemis, and ataxia-telangiectasia-mutated: signalling networks in DNA damage. Int J Biochem Cell Biol 40:598–603

    Article  PubMed  CAS  Google Scholar 

  73. Lavin MF, Kozlov S (2007) ATM activation and DNA damage response. Cell Cycle 6:931–942

    Article  PubMed  CAS  Google Scholar 

  74. Lo Muzio L, Sartini D, Santarelli A, Rocchetti R, Morganti S, Pozzi V, Rubini C, Bambini F, Emanuelli M. (2012) Expression and prognostic significance of apoptotic genes in oral squamous cell carcinoma. Mol Carcinog. doi:10.1002/mc.21960

  75. Lo Muzio L, Santarelli A, Emanuelli M, Pierella F, Sartini D, Staibano S, Rubini C, De Rosa G (2006) Genetic analysis of oral squamous cell carcinoma by cDNA microarrays focused apoptotic pathway. Int J Immunopathol Pharmacol 19:675–682

    PubMed  CAS  Google Scholar 

  76. Dunn SE, Hardman RA, Kari FW, Barrett JC (1997) Insulin-like growth factor 1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced by diverse anticancer drugs. Cancer Res 57:2687–2693

    PubMed  CAS  Google Scholar 

  77. Peretz S, Jensen R, Baserga R, Glazer PM (2001) ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response. Proc Natl Acad Sci USA 98:1676–1681

    Article  PubMed  CAS  Google Scholar 

  78. Resnicoff M, Abraham D, Yutanawiboonchai W, Rotman HL, Kajstura J, Rubin R, Zoltick P, Baserga R (1995) The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res 55:2463–2469

    PubMed  CAS  Google Scholar 

  79. Puzik A, Rupp J, Troger B, Gopel W, Herting E, Hartel C (2012) Insulin-like growth factor-I regulates the neonatal immune response in infection and maturation by suppression of IFN-gamma. Cytokine 60(2):369–376

    Article  PubMed  CAS  Google Scholar 

  80. Janke C, Rogowski K, Wloga D, Regnard C, Kajava AV, Strub JM, Temurak N, van Dijk J, Boucher D, van Dorsselaer A, Suryavanshi S, Gaertig J, Edde B (2005) Tubulin polyglutamylase enzymes are members of the TTL domain protein family. Science 308:1758–1762

    Article  PubMed  CAS  Google Scholar 

  81. Ikegami K, Horigome D, Mukai M, Livnat I, MacGregor GR, Setou M (2008) TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1. FEBS Lett 582:1129–1134

    Article  PubMed  CAS  Google Scholar 

  82. Kashiwaya K, Nakagawa H, Hosokawa M, Mochizuki Y, Ueda K, Piao L, Chung S, Hamamoto R, Eguchi H, Ohigashi H, Ishikawa O, Janke C, Shinomura Y, Nakamura Y (2010) Involvement of the tubulin tyrosine ligase-like family member 4 polyglutamylase in PELP1 polyglutamylation and chromatin remodeling in pancreatic cancer cells. Cancer Res 70:4024–4033

    Article  PubMed  CAS  Google Scholar 

  83. Lugering A, Lebiedz P, Koch S, Kucharzik T (2006) Apoptosis as a therapeutic tool in IBD? Ann N Y Acad Sci 1072:62–77

    Article  PubMed  Google Scholar 

  84. Marzetti E, Lees HA, Manini TM, Buford TW, Aranda JM Jr, Calvani R, Capuani G, Marsiske M, Lott DJ, Vandenborne K, Bernabei R, Pahor M, Leeuwenburgh C, Wohlgemuth SE (2012) Skeletal muscle apoptotic signaling predicts thigh muscle volume and gait speed in community-dwelling older persons: an exploratory study. PLoS ONE 7:e32829

    Article  PubMed  CAS  Google Scholar 

  85. Higami Y, Shimokawa I (2000) Apoptosis in the aging process. Cell Tissue Res 301:125–132

    Article  PubMed  CAS  Google Scholar 

  86. Boddaert J, Mallat Z, Fornes P, Esposito B, Lecomte D, Verny M, Tedgui A, Belmin J (2005) Age and gender effects on apoptosis in the human coronary arterial wall. Mech Ageing Dev 126:678–684

    Article  PubMed  CAS  Google Scholar 

  87. Colin A, Barroso G, Gomez-Lopez N, Duran EH, Oehninger S (2010) The effect of age on the expression of apoptosis biomarkers in human spermatozoa. Fertil Steril 94:2609–2614

    Article  PubMed  CAS  Google Scholar 

  88. Nooteboom M, Johnson R, Taylor RW, Wright NA, Lightowlers RN, Kirkwood TB, Mathers JC, Turnbull DM, Greaves LC (2010) Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts. Aging Cell 9:96–99

    Article  PubMed  CAS  Google Scholar 

  89. Kavathia N, Jain A, Walston J, Beamer BA, Fedarko NS (2009) Serum markers of apoptosis decrease with age and cancer stage. Aging 1:652–663

    PubMed  CAS  Google Scholar 

  90. Haberthur K, Engelman F, Barron A, Messaoudi I (2010) Immune senescence in aged nonhuman primates. Exp Gerontol 45:655–661

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Institute of General Medical Sciences (NIGMS) grant 8P20GM103538-09. We express our gratitude to the Caribbean Primate Research Center (CPRC) for its invaluable technical support.

Conflicts of interest

The authors report no conflicts of interest related to this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Octavio A. Gonzalez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gonzalez, O.A., John Novak, M., Kirakodu, S. et al. Effects of aging on apoptosis gene expression in oral mucosal tissues. Apoptosis 18, 249–259 (2013). https://doi.org/10.1007/s10495-013-0806-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-013-0806-x

Keywords

Navigation