Question

How important (quantitatively) is telomere length at birth to human longevity?

Answer 1

Telomeres are repetitive DNA consisting of hundreds of concatenated TTAGGG hexanucleotide sequences, located at the end of each human chromosome. Telomeres allow for preservation of the genome during replication and division. However, in most cells telomere sequences shorten with each cell replication to the extent that they are not repaired by telomerase, an enzymatic activity of variable presence in some cell types. On a cellular basis, reduction in telomere length is an indicator of cellular aging. Gradual loss of telomeric DNA in dividing somatic cells can contribute to replicative senescence or apoptosis. The loss of DNA from the telomeric cap protects the coding sequences from attrition and also limits cell replicative potential; once telomeres reach a critically shortened length, cells stop dividing and enter a state of replicative senescence . Progressive telomere shortening has been linked to both normal aging and to various degenerative diseases in a wide range of studies mainly in humans and mice, and telomere lengthening has been shown to have a restorative effect. It has been observed that in long-lived mammals, after embryogenesis, telomerase is down-regulated in most somatic tissues, which is thought to have evolved as a tumor-suppressing mechanism. Thus, telomere length is quite important at birth to human longevity.

Citations:

• Steenstrup, T., Kark, J. D., Verhulst, S., Thinggaard, M., Hjelmborg, J. V. B., Dalgård, C., … Aviv, A. (2017). Telomeres and the natural lifespan limit in humans. Aging (Albany NY), 9(4), 1130–1140. http://doi.org/10.18632/aging.101216
• Honig, L. S., Kang, M. S., Cheng, R., Eckfeldt, J. H., Thyagarajan, B., Leiendecker-Foster, C., … Schupf, N. (2015). Heritability of Telomere Length in a Study of Long-Lived Families. Neurobiology of Aging, 36(10), 2785–2790. http://doi.org/10.1016/j.neurobiolaging.2015.06.017
• Heidinger, B. J., Blount, J. D., Boner, W., Griffiths, K., Metcalfe, N. B., & Monaghan, P. (2012). Telomere length in early life predicts lifespan. Proceedings of the National Academy of Sciences, 109(5), 1743-1748.