Dear Tom –
This is my bailiwick, so I’m going to take a stab at answering your question.
Start with the statistical correlation between life expectancy and telomere length. Short telomeres are a predictor of mortality, independent of age. If two people are the same age and one has shorter telomeres, he is likely to die sooner. This is true for animals that have been studied, as well as humans.
Why would this be?
Telomeres get short when cells divide without telomerase. In that sense, short telomeres are a result of age (time gone by) but not of aging (senescence). I’ve never seen a coherent presentation of the view that senescence causes short telomeres. The closest I have heard is that when the body is challenged by something that calls for more cell division, then telomeres would get shorter. Infectious disease, injury, and exercise all lead to more cell division, but they don’t lead to shorter life spans, and in fact exercise leads to longer life span. I can’t see how any of these would explain a correlation between telomere length and life expectancy.
On the other side – do short telomeres cause higher mortality? Here there are several obvious mechanisms that suggest themselves:
Short telomeres lead to loss of stem cells and the renewal of tissue that they offer.
Short telomeres lead to senescent cells which increase inflammation in the body by emitting inflammatory cytokines.
Short telomeres lead to chromosome instability, double stranded breaks that can lead to cancer.
Short telomeres in hematopoietic stem cells reduces production of new white blood cells, contributing both to cancer and to vulnerability to infectious disease.
Finally, there is the direct empirical evidence:
removing cells with short telomeres increases mouse life span substantially.
giving aged mice a shot of telomerase increases their life expectanc and makes them healthy.
Convinced? If not, perhaps you can articulate the argument on the other side so I might better understand it.
On Mon, Mar 16, 2015 at 8:07 PM, Thomas Coote wrote:
IMO the fundamental question that has still not definitively been answered is:
Is telomere erosion causing aging or is it a result of aging?
If anyone can clear up that question then telomere restorative therapies might be the subject of more focus.
On Tuesday, March 17, 2015, steve hill wrote:
Ok so there have been experiments using Plasma in mice which has shown some rejuvenation and there have been experiments using mTERT to rejuvenate telomeres in mice to extend lifespan. However so far to my knowledge no one has attempted a combination of both therapies.
Most of us here would likely agree that increasing life and health span dramatically is likely going to need more than a single magic bullet. So I am wondering how well a combination of regenerative therapies might work.
Would mice with their differing Telomere mechanic be the best animal model? Could we use a knockout mouse with short telomeres to better test this and lengthen them via mTERT plus add young to old plasma to test this?
Could have a control group, an mTERT group, Plasma Group and one with both therapies to see which is better.