Food Science and Biotechnology

, Volume 27, Issue 2, pp 555–564 | Cite as

Inhibitory effect of vitamin C on intrinsic aging in human dermal fibroblasts and hairless mice

  • Jae-Hong Jeong
  • Mi-Bo Kim
  • Changhee Kim
  • Jae-Kwan HwangEmail author


Vitamin C significantly reduced senescence-associated β-galactosidase (SA-β-gal) activity, with both the suppression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulation of cell-cycle activators (E2F1 and E2F2). Vitamin C also effectively attenuated the hyperactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase-B (AKT) signaling pathway. The expression of the longevity marker, the mammalian target of rapamycin (mTOR), was down-regulated by vitamin C while the expressions of forkhead box O3a (FoxO3a) and sirtuin1 (SIRT1) were up-regulated by vitamin C. In the middle-aged (MA) mice, oral administration of vitamin C significantly inhibited wrinkle formation, skin atrophy, and loss of elasticity through increasing collagen and elastic fiber. The increase in transepidermal water loss and the decrease in skin hydration were recovered by vitamin C treatment in the MA mice. Overall, vitamin C effectively prevents cellular senescence in vitro and in vivo suggesting it has protective potential against natural aging of the skin.


Vitamin C Intrinsic aging Cellular senescence Hairless mice 



This work was supported by a Grant from the Kwang Dong Pharmaceutical Co., Ltd. (2013-8-1178).

Compliance with ethical standards

Conflict of interest

The authors declares that they have no conflict of interest.


  1. 1.
    Naylor EC, Watson RE, Sherratt MJ. Molecular aspects of skin ageing. Maturitas 69: 249–256 (2011)CrossRefGoogle Scholar
  2. 2.
    Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev. 24: 2463–2479 (2010)CrossRefGoogle Scholar
  3. 3.
    Gambino V, De Michele G, Venezia O, Migliaccio P, Dall’Olio V, Bernard L, Minardi SP, Fazia MAD, Bartoli D, Servillo G. Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging. Aging Cell 12: 435–445 (2013)CrossRefGoogle Scholar
  4. 4.
    Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8: 729–740 (2007)CrossRefGoogle Scholar
  5. 5.
    Nogueira V, Park Y, Chen CC, Xu PZ, Chen ML, Tonic I, Unterman T, Hay N. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell 14: 458–470 (2008)CrossRefGoogle Scholar
  6. 6.
    Miyauchi H, Minamino T, Tateno K, Kunieda T, Toko H, Komuro I. Akt negatively regulates the in vitro lifespan of human endothelial cells via a p53/p21-dependent pathway. EMBO J. 23: 212–220 (2004)CrossRefGoogle Scholar
  7. 7.
    Kim HK, Kim YK, Song IH, Baek SH, Lee SR, Kim JH, Kim JR. Down-regulation of a forkhead transcription factor, FOXO3a, accelerates cellular senescence in human dermal fibroblasts. J. Gerontol. A Biol. Sci. Med. Sci. 60: 4–9 (2005)CrossRefGoogle Scholar
  8. 8.
    Campisi J. Cellular senescence: putting the paradoxes in perspective. Curr. Opin. Genet. Dev. 21: 107–112 (2011)CrossRefGoogle Scholar
  9. 9.
    Ren JL, Pan JS, Lu YP, Sun P, Han J. Inflammatory signaling and cellular senescence. Cell. Signal. 21: 378–383 (2009)CrossRefGoogle Scholar
  10. 10.
    Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J. Am. Coll. Nutr. 22: 18–35 (2003)CrossRefGoogle Scholar
  11. 11.
    Farris PK. Topical vitamin C: a useful agent for treating photoaging and other dermatologic conditions. Dermatol. Surg. 31: 814–818 (2005)CrossRefGoogle Scholar
  12. 12.
    Kim J, Kim MB, Yun JG, Hwang JK. Protective effects of standardized Siegesbeckia glabrescens extract and its active compound kirenol against UVB-induced photoaging through inhibition of MAPK/NF-κB pathways. J. Microbiol. Biotechnol. 27: 242–250 (2016)CrossRefGoogle Scholar
  13. 13.
    Park JE, Woo SW, Kim MB, Kim C, Hwang JK. Standardized Kaempferia parviflora extract inhibits intrinsic aging process in human dermal fibroblasts and hairless mice by inhibiting cellular senescence and mitochondrial dysfunction. Evid. Based Complement. Altern. Med. 2017: 6861085 (2017)Google Scholar
  14. 14.
    Sikora E, Arendt T, Bennett M, Narita M. Impact of cellular senescence signature on ageing research. Ageing Res. Rev. 10: 146–152 (2011)CrossRefGoogle Scholar
  15. 15.
    Polager S, Ginsberg D. p53 and E2f: partners in life and death. Nat. Rev. Cancer 9: 738–748 (2009)CrossRefGoogle Scholar
  16. 16.
    Blagosklonny MV. Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans). Cell Cycle 9: 683–688 (2010)CrossRefGoogle Scholar
  17. 17.
    López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 153: 1194–1217 (2013)CrossRefGoogle Scholar
  18. 18.
    Brooks CL, Gu W. How does SIRT1 affect metabolism, senescence and cancer? Nat. Rev. Cancer 9: 123–128 (2009)CrossRefGoogle Scholar
  19. 19.
    Chung JH, Manganiello V, Dyck JR. Resveratrol as a calorie restriction mimetic: therapeutic implications. Trends Cell Biol. 22: 546–554 (2012)CrossRefGoogle Scholar
  20. 20.
    El-Domyati M, Attia S, Saleh F, Brown D, Birk D, Gasparro F, Ahmad H, Uitto J. Intrinsic aging versus photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Exp. Dermatol. 11: 398–405 (2002)CrossRefGoogle Scholar
  21. 21.
    Tagami H. Functional characteristics of the stratum corneum in photoaged skin in comparison with those found in intrinsic aging. Arch. Dermatol. Res. 300: 1–6 (2008)CrossRefGoogle Scholar
  22. 22.
    Farage MA, Miller KW, Elsner P, Maibach HI. Characteristics of the aging skin. Adv. Wound Care 2: 5–10 (2013)CrossRefGoogle Scholar
  23. 23.
    Kazlouskaya V, Malhotra S, Lambe J, Idriss MH, Elston D, Andres C. The utility of elastic Verhoeff-Van Gieson staining in dermatopathology. J. Cutan. Pathol. 40: 211–225 (2013)CrossRefGoogle Scholar
  24. 24.
    Uitto J. The role of elastin and collagen in cutaneous aging: intrinsic aging versus photoexposure. J. Drugs Dermatol. 7: s12-6 (2008)Google Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Jae-Hong Jeong
    • 1
  • Mi-Bo Kim
    • 1
  • Changhee Kim
    • 1
  • Jae-Kwan Hwang
    • 1
    Email author
  1. 1.Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeoulKorea

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