Re: [GRG] are short telomeres a cause or a result of aging?

Dear Josh,
Thank you for your detailed and well-constructed reply.
I have been rather busy this week and only just found time to reply.
For the sake of brevity, I will insert my comments in blue into your text below.

On Tue, Mar 17, 2015 at 4:46 AM, Josh Mitteldorf wrote:

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. 

This is, as you state, a correlation. Correlation does not equal causation. 

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.

In relation to these points I agree with the first 3, but reduction of WBC formation should lead to aplastic anaemia rather than cancer, I would have thought.

   Finally, there is the direct empirical evidence:

removing cells with short telomeres increases mouse life span substantially.

Do you mean removing senescent cells? If so, then perhaps the mouse LS is increased because the senescent cells were releasing deleterious factors such as inflammatory cytokines. Also, do you mean the treatment increased maximum LS or median LS?

giving aged mice a shot of telomerase increases their life expectanc and makes them healthy.

Again, are you referring to Blasco’s work? Blasco’s work (wonderful though it is) found an increase in median LS, not maximum LS when mice were given gene therapy via a viral vector.

Convinced? If not, perhaps you can articulate the argument on the other side so I might better understand it.

As you can see, no, I’m not yet convinced that telomerase inactivity or deficiency “causes” aging.

I am convinced that maintaining proper levels of functional telomerase is important for health and, by extension, healthspan.



PS: Is there any (anecdotal) evidence available from those who purchase and consume “telomerase activators”? Are their age biomarkers being reset to a more youthful state? Any information would be welcome.

– Josh

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.



About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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