An Interview with Michael Fossel
One of the roles of the enzyme telomerase is to extend the repeating telomere DNA sequences at the ends of chromosomes, thus lengthening the replicative life span of cells. Telomere length is a part of the clock mechanism limiting the life span of ordinary cells, and it decreases with each cell division. Telomerase is active in different tissues to different degrees, most notably in the stem cells that provide fresh cells with long telomeres to maintain tissues. The mix of these dynamics helps to determine the rate of cell turnover in any given tissue and the current average length of telomeres. This turnover rate varies greatly throughout the body, from a few days for the lining of the gut to essentially never for some of the central nervous system. The average length of telomeres tends to decline with aging or ill health, most likely due to a slowdown in the activity of stem cells and their delivery of new cells with long telomeres. As such these measures are probably a secondary aspect of aging, a marker rather than a root cause.
That said, increasing telomerase activity in mice has been shown to extend life, though there are several plausible reasons why this might be the case, only one of which involves enhanced tissue function due to longer-lived cells. The potential upside here has to be balanced with a concern over cancer: forcing cells into longer lives than evolution has settled on may or may not tip the balance in favor of much more cancer. This hasn't happened in the mouse studies, but mice have quite different telomere dynamics in comparison to humans.
Michael Fossel is one of the more noteworthy advocates for telomerase therapy as an important research direction for the treatment of aging. Here is an interview:
Michael Fossel's dream is to reverse human aging and since 1996 he has been a strong and vocal advocate of experimenting with telomerase therapy as a potential way of intervention in a wide variety of medical conditions related to aging. During our 1 hour discussion with Michael we cover a variety of interesting topics such as: his dream to reverse aging and the desirability and feasibility thereof; the Hayflick limit of cell division and Aubrey de Grey's concerns that telomerase therapy may cause cancer; the distinction between reversing aging and living forever; his "non-sexy" tips on healthy living; his take on cryonics and transhumanism."Ageing is dynamic, not static. Never mind the low-hanging fruit. [...] Go for the important one! The reason to [reverse aging] is not to double somebody's lifespan. The reason to do this is because people out there are hurting. They are frightened. They are terrified by the things that happen to them when they get disease. The reason to do this is because we are human and we should be working at this. It's not playing God, it is working at being human. It's compassion. It's not a matter of living longer, it is a matter of making people healthy again."
A very good interview indeed on the subject and good to see another aging researchers opinion.
On the negatives it seem to me that Michael Fossel is little bit too much of a concrete thinker and some of his semantic points on what aging is and what it isn't go into the philosophical spiral he talks about trying to avoid.
It was a good interview. Dr. Fossel's heart certainly seems to be in the right place. However, I wasn't fully satisfied with his response to Dr. de Grey's position. He accuses Dr. de Grey of "not reading" telomere research, but then he talks as though Dr. de Grey's approach to aging is centered upon mitochondria when that's just not the case at all. It seems as though Dr. Fossel has read Dr. de Grey's work on the mitochondrial theory of aging but nothing of his recent positions or the SENS approach, which is something of an irony given his accusation.
The Hayflick satellite analogy seems similar to the de Grey car analogy for conveying the damage-based theory, except that the car analogy leaves open the possibility of intervention while the satellite analogy does not. Simply pointing out that the human body is capable of some self-repair does not invalidate these analogies if in at least some respects the self-repair is absent or deficient and damage simply accumulates. The purpose of an analogy is to cast light on similarities, not to represent two things as being exactly identical. There are many examples of damage (lipofuscin, loss of pacemaker cells or neurons in brain areas other than the hippocampus) for which there is no evidence of ongoing repair.
On a more positive note, one can't help but be encouraged by Dr. Fossel's eagerness to move ahead with the proposed telomere interventions and validate them by demonstrating measurable abatement of age-related disease.
And what about TGF-β blocking hTERT?? TGF-β is greatly elevated by Senescence-Associated Secretory Phenotype. How would it be ever possible to lengthen telomeres in old people without lowering TGF-β? Senolytics are one of the more efficient ways to do it.