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

Harold,

 

Absolutely telomere length is not a function of cell divisions alone, though that is certainly one key factor. 

 

— From the Univ. of Utah School of Human Genetics (Richard Cawthon, et.al.): “In white blood cells, the length of telomeres ranges from 8,000 base pairs in newborns to 3,000 base pairs in adults and as low as 1,500 in elderly people. Each time it divides, an average cell loses 30 to 200 base pairs from the ends of its telomeres. Cells normally can divide only about 50 to 70 times, with telomeres getting progressively shorter until the cells become senescent or die. Telomeres do not shorten in tissues where cells do not continually divide, such as heart muscle.”

 

But the following also have a very significant impact on both telomere length and telomerase activity:

 

–Oxidative Stress can Reduce Telomerase Activity by 50-70% and Double the
Rate of Telomere Shortening. [Harley/Andrews/Blasco 2010; EH Blackburn 2010;
Kurz, 2004; T. von Zglinicki, 2002]

–Inflammation Accelerates the Rate of Telomere Shortening and Has a Major
Negative Impact on Telomerase Activity. [EH Blackburn, 2011; S. Bekaert, 2007, A. Aviv, 2009] 

–Inhibiting
the Inflammatory Cytokine TNF-alpha can actually Increase Telomerase Activity by 1.25 to
1.78-Fold, at least in vitro [RB Effros, 2009 &
2011]                                                                                                                                                                                                                                                                                                                                            
–Cortisol & and elevated Homocysteine can each Reduce Telomerase Activity by up to 50%, & each
increases the Rate of Telomere Shortening [EH Blackburn 2011; RB Effros 2008;
J. Zhu 2006; A. Aviv 2008]  (Per Rita Effros, cortisol “at the level of normal human stress” is sufficient to reduce telomerase activity by 50%.)

 

You state that “the cell has functional telomerase but doesn’t use it;” That would depend upon the cell type. While it is true that most human somatic cells do not express telomerase, or do so at very low levels:

— Lymphocytes
and some Adult Stem Cells, including hematopoietic stem cells (HSCs), are two of the
very few types of human somatic cells which
naturally express telomerase–due to their high replication and proliferative needs and capabilities–and they express
telomerase at relatively high levels, at least until they start to reach the point of
replicative senescence, at which point telomerase activity falls to low
levels. (Rita Effros, Experimental Gerontology 2011; C. Weyand & J.
Gorozny, Gerontology 2010)

 

–Per Lenhard Rudolph (Biochimie 90, 2008):
“Telomerase is active during embryogenesis but postnatally is
inactivated in most somatic tissues. Telomerase remains active in some stem
cell compartments such as hematopoietic stem cells (HSCs)  and intestinal
stem and progenitor cell in basal crypts. Telomerase activity in stem
cells is important to maintain the self-renewal of stem cells. However,
telomeres shorten in human HSCs during ageing suggesting that the level of
telomerase activity is not sufficient to maintain telomere length in ageing
stem cells…. These findings again indicate that human stem cells have
limited telomere reserves and are sensitive to telomere shortening during
ageing. It is conceivable that the gradual decline of stem cell function
contributes to human ageing. Although stem cells are defined by their
ability to self-renew, several lines of evidence suggest that adult stem cells
do age. Telomere shortening is one of the mechanisms that can limit the
self-renewal of HSC.”

 

— And per Maria Blasco: “Short
telomeres are causal of disease because when they are below a [certain]
length they are damaging for the cells. The stem cells of our tissues do not
regenerate and then we have ageing of the tissues.”  “These findings suggest that telomerase
activity and telomere length can directly affect the ability of stem cells to
regenerate tissues.” “Aging in mammals is associated with reduced stem cell activity in different organs, leading to
deficiencies in cell turnover and tissue
repair (Flores et al., 2006; Rando, 2006). Telomere maintenance
appears to be essential for the prolonged persistence of stem cell function in organs with extensive cell turnover.”  [MA Blasco, 2011 Interview; Nat Chem Biol.,
2007 Oct.;  Journal of Neuroscience, Nov.18, 2009]

 

 David

 

Telomere Biosciences, LLC.

David B. Cross

Founder & President

Cell: 917.370.7456 

http://ift.tt/1EfXQRl

 

 

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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. http://www.AgingIntervention.org 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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