Having kids wears you out? Same holds for telomeres. In zebra finches.

One of my most popular posts on the blog has been The Immortality Paradox, in which I discuss telomeres, aging, and cancer. Telomeres are the ends of he chromosomes, a bit of non-coding DNA that naturally wears off as cells divide and as we age. Once the telomeres reach a certain critical length the cell stops dividing and eventually dies. As a consequence, telomeres length varies across age groups but, even within the same age group, it varies from individual to individual. So, it becomes natural to ask: is this variation in telomeres length correlated to longevity?

A new study published in PNAS [1] seems to indicate that it is. Now, my personal disclaimer is that I'm always a little skeptical about associations with longevity because there are so many factors and confounders that it's really hard to extrapolate meaningful p-values. However, this study was done in birds (Taeniopygia guttata, or zebra finches), which makes it less prone to bias than a human study. In fact, the authors cite various studies that attempted to correlate telomeres length an longevity in humans but yielded mixed results. Most importantly, these earlier studies had not monitored telomeres length since an early stage in life, something that is critical in order to account for environmental factors that have been shown to accelerate telomere shortening.

In this study, Hedinger et al.

"examined telomere length in red blood cell samples from early in life (at 25 days) and at various points thereafter in a group of zebra finches (n = 99) that were allowed to live out their natural lifespan (ranging from 210 days to 8.7 years). We also examined the effect of reproduction on adult telomere length, by experimentally manipulating whether, and how often, individuals were allowed to breed. These data enabled us to uniquely examine the relationship between telomere dynamics from early in life and total lifespan and reveal that telomere length in early life is a highly significant predictor of the age of death."

While they found no differences between genders, Heidinger et al. did record a decrease in telomere length with age, which was most marked during the first year of life. Interestingly, they also found that telomere shortening was accelerated in birds engaging in reproduction. (When parents say kids make them age faster, they mean it!!) The effect, though, did not persist, and at the next time point the effect of reproduction on telomere length had weaned. Of course, the most interesting result was the significant correlation between telomere length in early life and lifespan. It is important to note that the highly significant correlation was with the measurement taken early in life: length measured at later time points didn't have such a strong predictive effect.

"We found telomere length at 25 days to be a very strong predictor of realized lifespan (P < 0.001); those individuals living longest had relatively long telomeres at all points at which they were measured. Reproduction increased adult telomere loss, but this effect appeared transient and did not influence survival. Our results provide the strongest evidence available of the relationship between telomere length and lifespan and emphasize the importance of understanding factors that determine early life telomere length."

The authors underline what still remains to be seen:

"Whether telomere length change itself plays a directly causative role in determining the pace of decline and age of death is an active area of research. Several mechanistic routes have been identified, mainly from in vitro studies, whereby shortened telomeres can accelerate aging and reduce longevity, primarily involving activation of cellular checkpoints of apoptosis, cell cycle arrest, and impaired stem cell and tissue function."

One thing is certain: any analogous study to be carried in humans should measure telomere length very early in life because, as this study shows, if individuals with shorter lengths die earlier, a sample of lengths measured later in life would already be skewed towards longer length (since individuals with shorter length would have already died) and hence the results would be inconclusive.

[1] Heidinger, B., Blount, J., Boner, W., Griffiths, K., Metcalfe, N., & Monaghan, P. (2012). Telomere length in early life predicts lifespan Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1113306109