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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 6292630, 11 pages
https://doi.org/10.1155/2017/6292630
Research Article

mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress

Department of Periodontology, School of Stomatology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai 200011, China

Correspondence should be addressed to Yufeng Xie; moc.liamtoh@eixgnefuy and Rong Shu; moc.liamtoh@321gnoruhs

Received 1 March 2017; Revised 27 April 2017; Accepted 3 May 2017; Published 19 July 2017

Academic Editor: Silvana Hrelia

Copyright © 2017 Yiru Xia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Christensen, G. Doblhammer, R. Rau, and J. W. Vaupel, “Ageing populations: the challenges ahead,” Lancet, vol. 374, no. 9696, pp. 1196–1208, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. S. M. Abdelmagid, M. F. Barbe, and F. F. Safadi, “Role of inflammation in the aging bones,” Life Sciences, vol. 123, pp. 25–34, 2015. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Hajishengallis, “Aging and its impact on innate immunity and inflammation: implications for periodontitis,” Journal of Oral Biosciences, vol. 56, no. 1, pp. 30–37, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. R. Stewart and M. West, “Increasing evidence for an association between periodontitis and cardiovascular disease,” Circulation, vol. 133, no. 6, pp. 549–551, 2016. View at Publisher · View at Google Scholar · View at Scopus
  5. C. A. Ramseier, J. S. Kinney, A. E. Herr et al., “Identification of pathogen and host-response markers correlated with periodontal disease,” Journal of Periodontology, vol. 80, no. 3, pp. 436–446, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. M. A. Reynolds, “Modifiable risk factors in periodontitis: at the intersection of aging and disease,” Periodontology 2000, vol. 64, no. 1, pp. 7–19, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. P. C. Smith, M. Caceres, C. Martinez, A. Oyarzún, and J. Martínez, “Gingival wound healing: an essential response disturbed by aging?” Journal of Dental Research, vol. 94, no. 3, pp. 395–402, 2015. View at Publisher · View at Google Scholar · View at Scopus
  8. L. Huang, B. Salmon, X. Yin, and J. A. Helms, “From restoration to regeneration: periodontal aging and opportunities for therapeutic intervention,” Periodontology 2000, vol. 72, no. 1, pp. 19–29, 2016. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Furukawa, K.-K. JR, M. Yamada, A. Senda, A. Manabe, and A. Miyazaki, “Cytotoxic effects of hydrogen peroxide on human gingival fibroblasts in vitro,” Operative Dentistry, vol. 40, no. 4, pp. 430–439, 2015. View at Publisher · View at Google Scholar · View at Scopus
  10. Q. Wang, M. Sztukowska, A. Ojo, D. A. Scott, H. Wang, and R. J. Lamont, “FOXO responses to Porphyromonas gingivalis in epithelial cells,” Cellular Microbiology, vol. 17, no. 11, pp. 1605–1617, 2015. View at Publisher · View at Google Scholar · View at Scopus
  11. S. C. Johnson, M. Sangesland, M. Kaeberlein, and P. S. Rabinovitch, “Modulating mTOR in aging and health,” Interdisciplinary Topics in Gerontology, vol. 40, pp. 107–127, 2015. View at Publisher · View at Google Scholar · View at Scopus
  12. S. C. Johnson, P. S. Rabinovitch, and M. Kaeberlein, “mTOR is a key modulator of ageing and age-related disease,” Nature, vol. 493, no. 7432, pp. 338–345, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. E. A. de Cavanagh, F. Inserra, and L. Ferder, “Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition,” American Journal of Physiology Heart and Circulatory Physiology, vol. 309, no. 1, pp. H15–H44, 2015. View at Publisher · View at Google Scholar · View at Scopus
  14. M. A. McCormick, J. R. Delaney, M. Tsuchiya et al., “A comprehensive analysis of replicative lifespan in 4, 698 single-gene deletion strains uncovers conserved mechanisms of aging,” Cell Metabolism, vol. 22, no. 5, pp. 895–906, 2015. View at Publisher · View at Google Scholar · View at Scopus
  15. X. Zeng, “Human embryonic stem cells: mechanisms to escape replicative senescence?” Stem Cell Reviews, vol. 3, no. 4, pp. 270–279, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. A. Bernadotte, V. M. Mikhelson, and I. M. Spivak, “Markers of cellular senescence. Telomere shortening as a marker of cellular senescence,” Aging (Albany New York), vol. 8, no. 1, pp. 3–11, 2016. View at Publisher · View at Google Scholar
  17. S. M. Phipps, J. B. Berletch, L. G. Andrews, and T. O. Tollefsbol, “Aging cell culture: methods and observations,” Methods in Molecular Biology, vol. 371, pp. 9–19, 2007. View at Google Scholar
  18. V. J. Cristofalo and R. Charpentier, “A standard procedure for cultivating human diploid fibroblastlike cells to study cellular aging,” Journal of Tissue Culture Methods, vol. 6, no. 3, pp. 117–121, 1980. View at Google Scholar
  19. K. J. Livak and T. D. Schmittgen, “Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method,” Methods, vol. 25, no. 4, pp. 402–408, 2001. View at Publisher · View at Google Scholar · View at Scopus
  20. M. V. Blagosklonny, “Koschei the immortal and anti-aging drugs,” Cell Death & Disease, vol. 5, 2014. View at Publisher · View at Google Scholar · View at Scopus
  21. P. A. Perez-Mancera, A. R. Young, and M. Narita, “Inside and out: the activities of senescence in cancer,” Nature Reviews Cancer, vol. 14, no. 8, pp. 547–558, 2014. View at Publisher · View at Google Scholar · View at Scopus
  22. C. D. Wiley, M. C. Velarde, P. Lecot et al., “Mitochondrial dysfunction induces senescence with a distinct secretory phenotype,” Cell Metabolism, vol. 23, no. 2, pp. 303–314, 2016. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Campisi and F. d'Adda di Fagagna, “Cellular senescence: when bad things happen to good cells,” Nature Reviews Molecular Cell Biology, vol. 8, no. 9, pp. 729–740, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. D. J. Baker, T. Wijshake, T. Tchkonia et al., “Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders,” Nature, vol. 479, no. 7372, pp. 232–236, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. D. E. Harrison, R. Strong, Z. D. Sharp et al., “Rapamycin fed late in life extends lifespan in genetically heterogeneous mice,” Nature, vol. 460, no. 7253, pp. 392–U108, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Bartke, “Pleiotropic effects of growth hormone signaling in aging,” Trends in Endocrinology and Metabolism, vol. 22, no. 11, pp. 437–442, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. R. M. Laberge, Y. Sun, A. V. Orjalo et al., “MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation,” Nature Cell Biology, vol. 17, no. 8, pp. 1049–1061, 2015. View at Publisher · View at Google Scholar · View at Scopus
  28. R. Iglesias-Bartolome, V. Patel, A. Cotrim et al., “mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis,” Cell Stem Cell, vol. 11, no. 3, pp. 401–414, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. N. Herranz, S. Gallage, M. Mellone et al., “mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype,” Nature Cell Biology, vol. 17, no. 9, pp. 1205–1217, 2015. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Laplante and D. M. Sabatini, “mTOR signaling in growth control and disease,” Cell, vol. 149, no. 2, pp. 274–293, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. Z. N. Demidenko, S. G. Zubova, E. I. Bukreeva, V. A. Pospelov, T. V. Pospelova, and M. V. Blagosklonny, “Rapamycin decelerates cellular senescence,” Cell Cycle, vol. 8, no. 12, pp. 1888–1895, 2009. View at Google Scholar
  32. M. Kolesnichenko, L. Hong, R. Liao, P. K. Vogt, and P. Sun, “Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence,” Cell Cycle, vol. 11, no. 12, pp. 2391–2401, 2012. View at Google Scholar
  33. C. Lerner, A. Bitto, D. Pulliam et al., “Reduced mammalian target of rapamycin activity facilitates mitochondrial retrograde signaling and increases life span in normal human fibroblasts,” Aging Cell, vol. 12, no. 6, pp. 966–977, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. N. Wei, H. Y. Hu, G. C. Xie et al., “Transcript and protein expression decoupling reveals RNA binding proteins and miRNAs as potential modulators of human aging,” Genome Biology, vol. 16, p. 41, 2015. View at Google Scholar
  35. E. Sahin and R. A. DePinho, “Axis of ageing: telomeres, p53 and mitochondria,” Nature Reviews Molecular Cell Biology, vol. 13, no. 6, pp. 397–404, 2012. View at Publisher · View at Google Scholar · View at Scopus
  36. C. A. Hinojosa, V. Mgbemena, S. Van Roekel et al., “Enteric-delivered rapamycin enhances resistance of aged mice to pneumococcal pneumonia through reduced cellular senescence,” Experimental Gerontology, vol. 47, no. 12, pp. 958–965, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. H. Wang, H. Zhou, X. Duan et al., “Porphyromonas gingivalis-induced reactive oxygen species activate JAK2 and regulate production of inflammatory cytokines through c-Jun,” Infection and Immunity, vol. 82, no. 10, pp. 4118–4126, 2014. View at Publisher · View at Google Scholar · View at Scopus
  38. C. J. Kenyon, “The genetics of ageing,” Nature, vol. 464, no. 7288, pp. 504–512, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. Z. Gong, O. Kennedy, H. Sun et al., “Reductions in serum IGF-1 during aging impair health span,” Aging Cell, vol. 13, no. 3, pp. 408–418, 2014. View at Publisher · View at Google Scholar · View at Scopus