Rate of Telomere Shortening Correlates with Species Average Life Span
Researchers here report on data showing a correlation between species life span and pace of telomere shortening. Telomeres are the repeated DNA sequences at the ends of chromosomes. A little is lost with each cell division, during replication of DNA, and cells with very short telomeres become senescent or self-destruct. This is how the vast majority of cells in the body are limited in their replicative capacity, in order to lower the risk of damaged cells becoming cancerous to an evolutionarily acceptable level. Not a personally acceptable level, of course.
With age, average telomere length tends to shorten in most species, and this is most likely a reflection of loss of stem cell function. Stem cells maintain long telomeres via use of telomerase, and thus the daughter somatic cells they provide to support surrounding tissue also have long telomeres. Given fewer such daughter cells, average telomere length diminishes, along with tissue function - but that loss of telomere length isn't the cause of loss of tissue function.
Nonetheless, telomerase gene therapy extends life in mice, most likely by inducing damaged cells to greater activity in tissue maintenance. Since the immune system is most likely improved as well, this treatment doesn't lead to a greater incidence of cancer, which would be the usual outcome of making damage cells do more work. This hypothesis on what takes place in telomerase gene therapy is still not a suggestion that telomere shortening is a cause of aging. In this view telomerase gene therapy is conceptually similar to stem cell therapies or signaling therapies that increase native cell activity without repairing the underlying damage that caused the decline. As noted in the publicity materials, this particular research group is generally in favor of the opposite viewpoint, that telomere shortening is an important causative mechanism of aging, rather than a largely downstream reflection of other issues.
Researchers discover that the rate of telomere shortening predicts species lifespan
After analyzing nine species of mammals and birds, researchers found a very clear relationship between the lifespan of these species and the shortening rate of their telomeres, the structures that protect the chromosomes and the genes they contain. The fit is better when using the average lifespan of the species - 79 years in the case of humans - rather than the maximum lifespan -the 122 documented years lived by the Frenchwoman Jeanne Calment.
Until now, however, no relationship had been found between telomere length and lifespan of each species. There are species with very long telomeres that are short-lived and vice versa. The researchers decided not to compare the absolute length of the telomeres, but rather their rate of shortening. It is the first large-scale study that compares this highly variable parameter between species: human telomeres lose on average about 70 base pairs - the building blocks of the genetic material - per year, whereas those of mice lose about 7,000 base pairs per year.
"This study confirms that telomeres play an important role in aging. There are people who are not convinced, and they say that for example mice live two years and have very long telomeres, while humans live much longer and have short telomeres; but we have shown that the important thing is not the initial length but the rate of shortening and this parameter predicts the longevity of a species with a high degree of precision."
Telomere shortening rate predicts species life span
Telomere shortening to a critical length can trigger aging and shorter life spans in mice and humans by a mechanism that involves induction of a persistent DNA damage response at chromosome ends and loss of cellular viability. However, whether telomere length is a universal determinant of species longevity is not known. To determine whether telomere shortening can be a single parameter to predict species longevities, here we measured in parallel the telomere length of a wide variety of species (birds and mammals) with very different life spans and body sizes, including mouse (Mus musculus), goat (Capra hircus), Audouin's gull (Larus audouinii), reindeer (Rangifer tarandus), griffon vulture (Gyps fulvus), bottlenose dolphin (Tursiops truncatus), American flamingo (Phoenicopterus ruber), and Sumatran elephant (Elephas maximus sumatranus).
We found that the telomere shortening rate, but not the initial telomere length alone, is a powerful predictor of species life span. These results support the notion that critical telomere shortening and the consequent onset of telomeric DNA damage and cellular senescence are a general determinant of species life span.
Blasco et al. keep putting out good papers with evidence that telomeres ARE causative in aging.
Reason on the other hand only has his opinon 'that loss of telomere length isn't the cause of loss of tissue function'; that 'telomerase gene therapy extends life in mice, most likely by inducing damaged cells to greater activity'; and that 'telomerase gene therapy is conceptually similar to stem cell therapies or signaling therapies that increase native cell activity without repairing the underlying damage that caused the decline'.
Where is the evidence for any of these statements?
Mark makes a valid point. While I agree with most of Reason's views, his position on telomere length appears to be unsupported. These articles concerning the rate of telomere shortening being predictive of lifespan do not provide any evidence of a causative connection, but that is not the point. The mere fact that there appears to be an associative connection is what matters. These two articles, coupled with a recent article provided by Reason which states (with strong evidence from several trials) that sufficient aerobic exercise can actually lengthen telomeres in humans, give us all hope for not just a healthier life, but a longer healthy life.
Blasco has a large body of work beyond this paper, which together gives significant evidence torwards telomeres being one (if not the main) driver of aging.
Unfortunately the aerobic exercise evidence for lengthening is nonsense IMO.
This really reinforces that telomere attrition is indeed a primary hallmark of aging. For years many people focused only on the total length and ignored any suggestion it was rate not length by people such as Michael Fossel etc...
This makes sense because as telomeres lose length they lose the ability to form loops and regulate various genes associated with aging via the TPE-OLD effect. In other words telomeres are like a fuse on a stick of dynamite, the faster they burn down the faster the gene expression changes via TPE-OLD and the more likely age-related diseases are due to the increased genomic and epigenomic instability caused. This is really the final nail in the coffin as I am concerned.
Agree Steve, for too long people have hidden behind the statistical noise inherent in leukocyte telomere length, whilst Fossel, Shay and Blasco have consistently made their arguments and patiently built their evidence. It really is overwhelming now.
Damage cannot be the 'underlying cause' of decline in a living system...
Damage is not the cause of cumulative damage...
Damage is not the cause of failure to detect, repair--and prevent--damage...
Abberations in underlying metabolism are the only possible causes of allowed damage...
It is unreasonable to claim that resultant damage, partially and temporarily mitigated as damage from outside the process, has anything whatsoever at all to do with addressing 'underlying causes'... The fact is entirely the reverse...