1. Fragility and Presbycusis
  2. Predisposing factors linked to presbycusis and balance disorders
  3. Genetic aspects: Telomeres and aging

Fragility and Presbycusis

Aging and the needs of older people: Health strategies for healthy aging

ISBN: 978-84-09-30541-4

Ángel Batuecas

Genetic aspects: Telomeres and aging

Introduction

Telomeres are special DNA sequences located at the ends of each chromosome. Metaphorically speaking, they are the adhesive at the tip of your shoelace that stops it from fraying. That is the main function of telomeres: stopping the DNA from breaking or damaging during mitosis over its lifetime.

Telomeres are exclusive to eukaryotic cells, and object of constant research about cell division, the lifespan of cells and cancer. Both their discovery in the 1930s and their molecular description in 2009 have been awarded the Nobel prize.

In humans, the sequence 5´TTAGGG 3´ is repeated up to 2,000 times at the end of the chromosome and marks its end1.

As telomeres mark the end of the chromosome, they prevent the chromosome tips from mixing up and help homologous chromosomes pair during meiosis. The telomeres divide and shorten by some 30 to 200 base pairs with each mitosis, until they have shortened to an extent that prevents the cell from dividing again, as DNA integrity cannot be guaranteed2. It is a biological clock of sorts. The size of the telomeres indicates cell age.

Indeed, telomeres are valuable and transcendent in cancer research: they do not shorten in tumor cells despite repeated mitosis.

Link between the Size of Telomeres and the Risk of Age-Related Hearing Loss.

In 2002, Seidman3 established that changes to telomeres can predispose towards age-related hearing loss. There is a direct relation between oxidative stress and the size of telomeres and an inverse relation between the size of telomeres and age4.

The first research associating age-related sensorineural hearing loss with oxygen-reactive species (free radicals than can produce oxidative damage) was conducted on animals5.

This research laid the foundation to show that oxidative stress is the link between age-related hearing loss and the shortened telomeres6.

Shortened telomeres in hearing-loss patients has been proven by analyzing age-related hearing loss in patients over age 70 and controls over age 70 without hearing loss. Shortened telomeres are observed for different types of hearing loss, both pantonal hearing loss and those starting at 2000 Khz, or mild hearing loss. It is not the case of patients with hearing loss in the 8000Hz range only7.

The link between hearing loss and shortened telomeres has only been established for age-related hearing loss. It has not been proven in young, adolescent, and middle-age patients with hearing loss. In fact, there have been no differences in telomere length found between hearing impaired parents and their children8.

References

  1. Moyzis, R. K. et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proceedings of the National Academy of Sciences of the United States of America. 1988; 85: 6622–6626.
  2. Shay JW, Wright WE. Hayflick, his limit, and cellular ageing. Nature reviews. Molecular cell biology. 2000; 1: 72–76, doi:10.1038/35036093
  3. Seidman MD, Ahmad N, Bai U. Molecular mechanisms of age-related hearing loss. Ageing research reviews. 2002; 1: 331–343.
  4. Sampson MJ, Winterbone MS, Hughes JC, Dozio N, Hughes DA. Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes. Diabetes care.2006; 29: 283–289.
  5. Someya S, Xu J, Kondo K, Ding D, Salvi RJ, Yamasoba T, Rabinovitch PS, Weindruch R, Leeuwenburgh C, Tanokura M, Prolla TA. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106: 19432–19437, doi:10.1073/pnas.0908786106.
  6. von Zglinicki, T., Burkle, A. & Kirkwood, T. B. Stress, DNA damage and ageing–an integrative approach. Experimental gerontology. 2001; 36: 1049–1062.
  7. Liu H, Luo H, Yang T, Wu H, Chen D. Association of leukocyte telomere length and the risk of age-related hearing impairment in Chinese Hans. Sci Rep. 2017; 7: 10106.
  8. Wang J, Nguyen MT, sung V, Grobler A, Burgner D, Saffery R, Wake M. Associations between telomere length and hearing status in mid-childhood and mildlife: population-based cross-sectional study. Ear Hearing. 2019; 40: 1256-1259.