Aging Voice pp 109-115 | Cite as

Future Prospects



The aging voice has complex issues including deterioration of the respiratory system, the vocal fold, resonant organs, muscle, posture, energy, etc. Once the voice is aged, it is often difficult to treat with current strategies, such as voice therapy and augmentation of the vocal fold. Prevention of voice aging is important, and anti-aging or preemptive medicine will be needed in the future. Caloric restriction (CR) is the most reproducible maneuver for extending lifespan. It is suggested that CR might activate sirtuin gene/protein, the main regulator of lifespan, which regulates cell repair, antioxidant effects, and apoptosis. Resveratrol (RSV) has been reported to be a CR mimetic driven by Sirtuin1 activation. RSV has a broad spectrum of activities that are beneficial to health, and may serve as a therapeutic or as an adjuvant agent in age-related voice disorders. Oxidative stress has a great impact on aging, and over-expression of reactive oxygen species is revealed to contribute to age-related histological changes of the vocal fold. It has also been proven that astaxanthin, a strong antioxidant, prevents age-related atrophy of the vocal fold. There are still many unclear aspects regarding the factors that affect voice aging that should be resolved in the future. Regenerative medicine should be useful in recovering the function of aged vocal folds. Currently, basic fibroblast growth factor is clinically usable, and positive effects on the regeneration of the vocal fold have been reported. Further improvements in regenerative medicine for the aged voice are needed.


Hyaluronic Acid Hepatocyte Growth Factor Caloric Restriction Regenerative Medicine Vocal Fold 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Imura H. Life course health care and preemptive approach to non-communicable diseases. Proc Jpn Acad Ser B Phys Biol Sci. 2013;89(10):462–73.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300.CrossRefPubMedGoogle Scholar
  3. 3.
    Mizuta M, Hirano S, Ohno S, et al. Expression of reactive oxygen species during wound healing of vocal folds in a rat model. Ann Otol Rhinol Laryngol. 2012;12:804–10.CrossRefGoogle Scholar
  4. 4.
    Mizuta M, Hirano S, Hiwatashi N, et al. Effect of astaxanthin on age-associated changes of vocal folds in a rat model. Laryngoscope. 2014;124(10):E411–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Mizuta M, Hirano S, Hiwatashi N, et al. The effect of astaxanthin on vocal fold wound healing. Laryngoscope. 2014;124:E1–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004;305:390–2.CrossRefPubMedGoogle Scholar
  7. 7.
    Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell. 2006;124:315–29.CrossRefPubMedGoogle Scholar
  8. 8.
    Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012;483:218–21.CrossRefPubMedGoogle Scholar
  9. 9.
    Sack MN, Finkel T. Mitochondrial metabolism, sirtuins, and aging. Cold Spring Harb Perspect Biol. 2012;4(12). pii: a013102. doi: 10.1101/cshperspect.a013102.
  10. 10.
    Guarente L. Calorie restriction and sirtuins revisited. Genes Dev. 2013;27(19):2072–85. doi: 10.1101/gad.227439.113.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Colman RJ, Beasley TM, Kemnitz JW, et al. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun. 2014;5:3557. doi: 10.1038/ncomms4557.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Masoro EJ. Caloric restriction and aging: an update. Exp Gerontol. 2000;35(3):299–305.CrossRefPubMedGoogle Scholar
  13. 13.
    Civitarese AE, Carling S, Heilbronn LK, et al. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med. 2007;4:e76.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bellaver B, Bobermin LD, Souza DG, et al. Signaling mechanisms underlying the glioprotective effects of resveratrol against mitochondrial dysfunction. Biochim Biophys Acta. 2016;1862(9):1827–38. doi: 10.1016/j.bbadis.2016.06.018.CrossRefPubMedGoogle Scholar
  15. 15.
    Gweon EJ, Kim SJ. Resveratrol attenuates matrix metalloproteinase-9 and -2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways. Oncol Rep. 2014;32(1):71–8. doi: 10.3892/or.2014.3192.CrossRefPubMedGoogle Scholar
  16. 16.
    Stojanovic S, Sprinz H, Brede O. Efficiency and mechanism of the antioxidant action of trans-resveratrol and its analogues in the radical liposome oxidation. Arch Biochem Biophys. 2001;391:79–89.CrossRefPubMedGoogle Scholar
  17. 17.
    Brito P, Almeida LM, Dinis TC. The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection against LDL oxidation. Free Radic Res. 2002;36:621–31.CrossRefPubMedGoogle Scholar
  18. 18.
    Ryan MJ, Jackson JR, Hao Y, et al. Suppression of oxidative stress by resveratrol after isometric contractions in gastrocnemius muscles of aged mice. J Gerontol A Biol Sci Med Sci. 2010;65A(8):815–31. doi: 10.1093/gerona/glq080.
  19. 19.
    Wu H, Li GN, Xie J, et al. Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-β/periostin pathway in STZ-induced diabetic mice. BMC Cardiovasc Disord. 2016;16:5. doi: 10.1186/s12872-015-0169-z.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Huang P, Riordan SM, Heruth DP, et al. A critical role of nicotinamide phosphoribosyltransferase in human telomerase reverse transcriptase induction by resveratrol in aortic smooth muscle cells. Oncotarget. 2015;6(13):10812–24.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lortie CL, Rivard J, Thibeault M, et al. The moderating effect of frequent singing on voice aging. J Voice. 2016;31:112.e1–e12. doi: 10.1016/j.jvoice.2016.02.015.
  22. 22.
    Hirano S, Tateya I, Kishimoto Y, et al. Clinical trial of regeneration of aged vocal folds with growth factor therapy. Laryngoscope. 2012;122:327–31.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Otolaryngology Head and Neck SurgeryKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Tazuke Kofukai, Medical Research Institute, Department of Otolaryngology, Head and Neck SurgeryKitano HospitalOsakaJapan
  3. 3.The Foundation of Biomedical Research and Innovation, Translational Research Informatics CenterKobeJapan

Personalised recommendations