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

Dear Walt, Tom, Josh, David, Harold, and others participating in the telomere discussion.

When I read through your comments on telomeres, I did not see much mentioned about the molecular biology 

of telomeres that has been discovered in the past 5-10 years.
Here is a short summary of the 15 major molecular mechanisms that affect/regulate telomere length

which have not been discussed much on LA-GRG. (I purposely left off telomerase and hTERC,

which has been discussed at length).

I did not order them in order of importance (all of these discoveries are important).

Instead, I hope each of these major molecular mechanisms controlling telomere length will inspire each

of you to learn more and share with us what you learned. (please share what you learned with me).

I think we must “move on” from a simple discussion of “telomerase activation” to that of a much larger view

of what controls telomeres, which includes long non-coding RNA (TERRA), histone trimethylation (H3K9 and H4K20),

COMPASS (H3K4me3), histone H3K79 trimethylation, histone hyperacetylation, Rb proteins, subtelomeric DNA

methylation (DNMTs), the miR-290 family, Shelterin proteins, Rap-1, SIRT1, Tankyrases, SIRT6, and the ALT

mechanism are all very important aspects of telomere length control.

It is NOT all due to the enzyme telomerease or the p53-mediated DNA-damage response (DDR).

Here are the “top 15” things that I have not seen LA-GRG members discussing much about:

1. Both ends of the chromosome arm are important for lifespan!

Each chromosome arm as two ends – the pericentromeric area and the telomeric area. Both must be silenced

by the formation of heterochromatin.  Pericentromeric heterochromatin (pericentromere DNA) and the telomeric

heterochromatin  are both equally important in lifespan!  Disruptions in histone protein modifications and with DNA

methylation in the pericentromeric region result in chromosomal instability, recombination, and aneuploidy.  In old

age, as many as 80% of cells display features of aneuploidy in organs like the liver.  Disruptions in histone protein 

modifications and with DNA methylation of the subtelomeric regions likewise regulated telomere length and the ALT 

pathway.  I noted that LA-GRG discussions on telomere length rarely mentions pericentromeric DNA stability.  Instability

in this area is a major factor in the development of aneuploidy, cancer, and aging. Let’s include in the discussion of the

“end of the chromosome arm” more information about the “beginning of the chromosome arm”. 


Here is an illustration that compares the silencing mechanism of the “end of the chromosome arm” and the “pericentromeric DNA”

Ref for illustration:

About Johnny Adams

My full-time commitment is to slow and ultimately reverse biological aging and age related decline for more years of healthy living. 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 Aging Intervention Foundation (dba for Carl I. Bourhenne Medical Research 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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