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Nathan Goodyear

Telomerase at the intersection of cancer and aging - 0 views

www.ncbi.nlm.nih.gov/...PMC3896987

telomere telomeres telomerase telomerase activator aging disease cancer

shared by Nathan Goodyear on 18 May 16 - No Cached
  • The anti-aging role of telomerase has been demonstrated to be largely mediated by its canonical role in elongating telomeres, which prevents the accumulation of critically short telomeres and loss of tissue homeostasis
  • Short telomeres, and subsequent DDR activation, could occur both in cancer and aging
  • increased abundance of short telomeres correlates with higher genomic instability and decreased longevity in various organisms, including mice, zebrafish, and yeast
  • ...15 more annotations...
  • mice deficient for telomerase or for telomere binding proteins are characterized by accelerated age-related defects
  • In humans, short telomeres are considered good indicators of an individual’s health status and correlate with both genetic and environmental factors
  • Although recent findings strongly support the idea that short telomeres drive several age-related diseases 38 we cannot exclude the possibility that in some situations short telomeres may be a consequence of the disease itself.
  • the current view is that telomerase deficiency may contribute to the early steps of cancer development by fueling chromosomal instability, while subsequent activation of telomerase may be necessary to allow tumor growth and tumor progression towards more malignant states
  • telomerase activation can be an early event in cancer, it is not necessary for cancer initiation
  • telomerase can stimulate tumor progression by ensuring maintenance of telomeres above a critically short length, thus preventing induction of cellular senescence or apoptosis
  • Almost all human cancers present activation of telomerase as a hallmark, most likely as a mechanism to allow unlimited cell proliferation of tumor cells
  • recent evidence demonstrated that short telomeres alone could lead to genomic instability and cancer
  • Getting rid of telomerase can also be problematic; the lack of telomerase could lead to increased chromosomal instability, which in turn could be at the basis for cancer initiation when tumor suppressor barriers are bypassed
  • telomerase activation is a potential therapeutic strategy for the treatment of age-related diseases
  • telomerase activation in adult or old mice by means of a gene therapy strategy was shown to be sufficient to improve metabolic fitness, neuromuscular capacity, and prevent bone loss, as well as significantly increase both median and maximum longevity, without increased cancer incidence
  • These studies suggest that telomerase expression could be considered a feasible approach to reverse tissue dysfunction and extend healthy lifespan without increasing cancer incidence
  • humans almost completely lose telomerase activity from somatic tissues in the adulthood
  • a change of paradigm seems to be occurring in telomerase biology, with a switch from viewing telomerase as fueling cancer to reversing aging
  • Telomerase expression in a background of high levels of tumor suppressors or in aged organisms seems to prevent its expected pro-cancer activity and yet it still functions as an anti-aging factor
  • Nathan Goodyear on 18 May 16
     
    Telomerase activity and longer telomere length is shown to correlated inversely with many chronic diseases of aging.  In contrast, telomerase activity is found to be involved in carcinogenesis.  Increased carcinogenic potential of telomerase activity has not borne out in studies.  In addition, increased CD8 cell activity as a result of telomerase activation will actually decrease carcinogenic potential via NK activation.
Nathan Goodyear

The telomerase activator TA-65 elongates short telomeres and increases health span of a... - 0 views

www.ncbi.nlm.nih.gov/...PMC3627294

TA-65 telomere Telomerase telomerase activator aging natural wellness health

shared by Nathan Goodyear on 16 May 16 - No Cached
  • studies have demonstrated that the shortest telomeres are causal of reduced cell viability
  • a stable and enforced expression of telomerase leads to an improved health-span, accompanied by an extension of lifespan
  • TA-65 influences the percentage of cellular short telomeres through the activation of telomerase
  • ...17 more annotations...
  • TA-65 administration during 4 months significantly improved the capacity to uptake glucose after a glucose pulse
  • liver protective action of TA-65
  • A disadvantage of mTERT potentiation could be associated to its capacity to favor proliferation of cancerous cells in murine models
  • TA-65 treated mice presented a similar incidence of malignant cancers at time of death, with a tendency to show decreased sarcomas and slightly increased lymphomas
  • We demonstrate here that TA-65 leads to a significant rescue of short telomeres through telomerase activation
  • TA-65 treatment increases proliferation and mobilization potential of mouse keratinocytes in vitro, a situation mimicking telomerase overexpression
  • TAT2, a similar molecule, have beneficial effects in the activation of CD8+ T lymphocytes from HIV-infected patients where they observe an increase of the proliferative potential and enhancement of cytokine/chemokine production
  • TA-65 resulted in a similar rescue of short telomeres in leukocytes post-treatment as observed with humans, most likely through an activation of telomerase
  • we observe that TA-65 lead to 10 fold increase of telomerase RNA levels in the liver of treated mice comparing to the non-treated same-age cohorts
  • TA-65 regulates telomerase at the transcription level, probably through the regulation of the MAPK pathway
  • TA-65 dependent telomerase activation results in a better organ fitness as demonstrated by the improved scores at the glucose tolerance test and insulin levels at fasting
  • TA-65 supplemented mice also present modest enhancement of the subcutaneous and epidermal thickness, as well as higher bone density, representative of an overall fitness status improvemen
  • TA-65 treated mice present higher levels of RBC and hemoglobin comparing to the control cohorts
  • improved health-span of TA-65 treated mice is not accompanied by increased cancer incidence, which may be related to the fact that TERT levels are very modestly increased in all tissues tested except for the liver
  • systemic telomerase overexpression from the germline leads to protection from aging associated pathologies
  • similar situation could be mimicked expressing telomerase late in life in a telomerase deficient background
  • we observed a higher proliferation rate and a partial protection from cell death in some tissues of TA65 treated mice
  • Nathan Goodyear on 16 May 16
     
    TA-65 shown to increase telomerase activity, and thus telomere length of short telomeres, in mouse study.  
Nathan Goodyear

aging - Telomere Science Library - 0 views

www.telomerescience.com/...aging

Telomere length ageing disease

shared by Nathan Goodyear on 19 Jul 11 - No Cached
  • Nathan Goodyear on 19 Jul 11
     
    great resource for Telomere research.  Telomere shortening is clearly associated with aging and age related diseases.  Further research continues on the role played by Telomeres in ageing related diseases
Nathan Goodyear

Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in ... - 0 views

www.genetics.org/...1061.long

telomere telomeres disease aging health

shared by Nathan Goodyear on 18 May 16 - No Cached
  • Nathan Goodyear on 18 May 16
     
    epidemiological study finds that telomere length inversely correlated with longevity, especially in those > 75.  The sex differences was significant beyond the age of 50, with women having longer telomere lengths.
Nathan Goodyear

Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Pr... - 0 views

cancerdiscovery.aacrjournals.org/...1130.abstract

Telomere length prostate cancer

shared by Nathan Goodyear on 10 Jan 14 - No Cached
  • Nathan Goodyear on 10 Jan 14
     
    The longer the telomere length, the less aggressive prostate cancer appears to be.  In fact, this study found that those with the longest Telomere length had a 87% lower risk of death from prostate cancer.
Nathan Goodyear

Association of Leukocyte Telomere Length With Breast Cancer Risk: Nested Case-Control F... - 0 views

aje.oxfordjournals.org/...aje.kws291.full

telomere telomeres telomerase cancer women breast breast cancer

shared by Nathan Goodyear on 17 Mar 14 - No Cached
  • Nathan Goodyear on 17 Mar 14
     
    Shorter telomere lengths associated with breast cancer.  But, longer telomere length may as well.
Nathan Goodyear

Telomere shortening and ageing of the immune system | Mendeley - 0 views

www.mendeley.com/...-ageing-of-the-immune-system-1

Telomere immmune system disease length ageing

shared by Nathan Goodyear on 19 Jul 11 - No Cached
  • The immune system is highly sensitive to shortening of telomeres
  • they can up-regulate telomerase, the telomere extending enzyme
  • In ageing immune system adaptive immunity deteriorates because of a progressive decline of naive T and B cells and decrease of absolute numbers of T and B lymphocytes
  • Nathan Goodyear on 19 Jul 11
     
    the immune system is very sensitive to shortening of telomere length. This change in the immune system can be a pivotal role in disease development
Nathan Goodyear

Plasma irisin levels predict telomere length in ... [Age (Dordr). 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24469890

telomere Irisin hormone hormones metabolism exercise

shared by Nathan Goodyear on 13 Mar 14 - No Cached
  • Nathan Goodyear on 13 Mar 14
     
    Irisin is a new hormone found to play a role in energy metabolism.  Irisin levels are predictive of telomere length i.e. the higher the irisin levels, the longer the telomere lengths.
Nathan Goodyear

Telomere length analysis in Cushing's syndr... [Eur J Endocrinol. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24743394

Telomere Cortisol hormone hormones Cushing's syndrome

shared by Nathan Goodyear on 23 Jun 14 - No Cached
  • Nathan Goodyear on 23 Jun 14
     
    Telomere length is shorter in active Cushing's syndrome compared to inactive Cushing's syndrome.  This suggests that elevated Cortisol is associated with shorter Telomere length.
Nathan Goodyear

Telomere Length Trajectory and Its Determinants in Persons with Coronary Artery Disease... - 0 views

www.telomerescience.com/...-from-the-heart-and-soul-study

Telomere length cardiovascular disease CVD

shared by Nathan Goodyear on 19 Jul 11 - No Cached
  • Nathan Goodyear on 19 Jul 11
     
    telomere length may play a role in cardiovascular disease development
Nathan Goodyear

Greater Lifetime Pesticide Use Causes Telomere Shortening - 0 views

www.greenmedinfo.com/...e-causes-telomere-shortening-0

pesticide toxins toxicants pesticides Telomere

shared by Nathan Goodyear on 02 Jul 13 - No Cached
  • Nathan Goodyear on 02 Jul 13
     
    Hard to show causation here, but volume of environmental toxicants associated with shortening of Telomeres.  Mechanism?  Increased free radical induced mitochondrial disruption resulting in relocation of the Telomerase enzyme from the mitochondria to the nuclei.   This has been shown to occur in cancer pathogenesis.
Nathan Goodyear

A possible new mechanism in the pathophysiology of polycystic ovary syndrome: The disco... - 0 views

jcem.endojournals.org/...jc.2013-3685.abstract

PCOS telomere telomeres polycystic ovary syndrome

shared by Nathan Goodyear on 09 Dec 13 - No Cached
  • Nathan Goodyear on 09 Dec 13
     
    shorter Telomere length associated with PCOS.
Nathan Goodyear

Physical activity and telomere length in U.S. men and women: An NHANES investigation - 0 views

www.sciencedirect.com/...S0091743517301470

Telomere Telomeres exercise

shared by Nathan Goodyear on 26 May 17 - No Cached
  • Nathan Goodyear on 26 May 17
     
    longer Telomere lengths in those with regular exercise beyond the age of 40.
Nathan Goodyear

A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized, Dou... - 0 views

online.liebertpub.com/...rej.2015.1793

TA-65 Telomerase telomerase activator Telomeres aging wellness health natural

shared by Nathan Goodyear on 16 May 16 - No Cached
  • Nathan Goodyear on 16 May 16
     
    low dose TA-65, which is a telomerase activator found to significantly lengthen Telomeres in human randomized study.
Nathan Goodyear

Telomerase reactivation reverses tissue degeneration in aged telomerase deficient mice - 0 views

www.ncbi.nlm.nih.gov/...PMC3057569

telomerase telomerase activator telomere aging

shared by Nathan Goodyear on 18 May 16 - No Cached
  • age-progressive loss of telomere function in mice has been shown to provoke widespread p53 activation resulting in activation of cellular checkpoints of apoptosis, impaired proliferation and senescence, compromised tissue stem cell and progenitor function, marked tissue atrophy and physiological impairment in many organ systems
  • Despite chromosomal instability, the brief course of telomerase reactivation was not sufficient to promote carcinogenesis (data not shown), a finding consistent with a role for telomerase in promoting progression of established neoplasms
  • Nathan Goodyear on 18 May 16
     
    another mouse study that found that increasing telomerase activity in shortened telomere mice improved tissue regeneration.
Nathan Goodyear

Are Short Telomeres Predictive of Advanced Cancer? - 0 views

cancerdiscovery.aacrjournals.org/...1096.abstract

Telomere length prostate cancer

shared by Nathan Goodyear on 10 Jan 14 - No Cached
  • Nathan Goodyear on 10 Jan 14
     
    Telomere length useful as a prognostic marker in prostate cancer as well as in predicting risk.
Nathan Goodyear

Access : Shorter telomeres are associated with obesity and weight gain in the elderly :... - 0 views

www.nature.com/...ijo2011196a.html

Telomere obesity

shared by Nathan Goodyear on 09 Sep 13 - No Cached
  • Nathan Goodyear on 09 Sep 13
     
    shorter Telomere length associated with obesity in the elderly.
Nathan Goodyear

Testosterone therapy delays cardiomyocyt... [Braz J Med Biol Res. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21971687

Testosterone Telomere Telomeres CVD heart AR aging estradiol low T

shared by Nathan Goodyear on 03 Mar 14 - No Cached
  • Nathan Goodyear on 03 Mar 14
     
    Study finds that low Testosterone contributes to cardiomyocyte agine in mouse model.  Low Testosterone was associated with a shorter telomere length.  "Physiologic" Testosterone therapy slowed this aging effect of the cardiomyocyte via an AR independent pathway as the Tfm mice have nonfunctional AR.  The authors propose that it may be via aromatase activity.
Nathan Goodyear

Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice ... - 0 views

www.nature.com/...nature09603.html

Telomere aging anti-aging telomerase bioidentical

shared by Nathan Goodyear on 08 Dec 10 - No Cached
  • marked reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.
  • Nathan Goodyear on 08 Dec 10
     
    Telomere lengthening reverses tissue degeneration; true anti-aging
Nathan Goodyear

Leukocyte Telomere Length and Mortality in the Cardiovascular Health Study - 0 views

biomedgerontology.oxfordjournals.org/...421.abstract

Telomere aging

shared by Nathan Goodyear on 18 May 11 - No Cached
  • Nathan Goodyear on 18 May 11
     
    Telomere length weakly correlated with mortality rate
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