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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

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

Effects of androgens on telomerase activity in normal and malignant prostate cells in v... - 0 views

onlinelibrary.wiley.com/...AC2C88175F4E55359BA67DC.f03t03

androgen deprivation therapy Prostate cancer androgen deprivation therapy Testosterone Telomerase Telomere length

shared by Nathan Goodyear on 10 Jan 14 - No Cached
  • Nathan Goodyear on 10 Jan 14
     
    Androgen deprivation therapy reduces Telomerase activity in androgen dependent prostate cancer cell lines.  Conversely, Testosterone increases Telomerase activity.  In these cell lines Telomerase activity is positively associated with prostate cancer.
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

A Natural Product Telomerase Activator As Part of a Health Maintenance Program - 0 views

www.ncbi.nlm.nih.gov/...PMC3045570

TA-65 natural telomere Telomerase telomerase activator aging wellness health

shared by Nathan Goodyear on 16 May 16 - No Cached
  • Nathan Goodyear on 16 May 16
     
    TA-65, from astragalus, shown to up regulate telomerase activity to increase telomere length to a statistical level.
Nathan Goodyear

Cells | Free Full-Text | Functional Assessment of Pharmacological Telomerase Activators... - 0 views

www.mdpi.com/57

TA-65 telomere telomerase activator Telomerase aging natural wellness health

shared by Nathan Goodyear on 16 May 16 - No Cached
  • Nathan Goodyear on 16 May 16
     
    TA-65 found to significantly increase telomerase activity in cell culture.
Nathan Goodyear

Activation of p53, inhibition of telomerase activity and induction of estrogen receptor... - 0 views

www.ncbi.nlm.nih.gov/...PMC555559

ER-beta breast cancer telomerase estrogen receptor estrogen receptor

shared by Nathan Goodyear on 23 Nov 12 - No Cached
  • Nathan Goodyear on 23 Nov 12
     
    ER-beta found to inhibit growth and telomerase activity in breast cancer.
Nathan Goodyear

Resveratrol reduces endothelial progenitor cells senescence through augmentation of tel... - 0 views

www.ncbi.nlm.nih.gov/...PMC2567879

resveratrol EPCs ageing endothelial progenitor cells Telomere Telomerase activity

shared by Nathan Goodyear on 11 Jul 12 - No Cached
  • Nathan Goodyear on 11 Jul 12
     
    Resveratrol reduces EPC ageining through increased Telomerase activity, and thus increasing telomere length.  Estradiol has been shown to do the same.
Nathan Goodyear

Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How ca... - 0 views

www.nature.com/...1205163a.html

Telomerase activity Telomere length cancer

shared by Nathan Goodyear on 10 Jan 14 - No Cached
  • Nathan Goodyear on 10 Jan 14
     
    Good discussion of Telomerase activity and cancer.
Nathan Goodyear

Curcumin inhibits telomerase activity in human cancer cell lines - 0 views

www.spandidos-publications.com/...227

Curcumin Tumeric Telomerase Telomere length cancer

shared by Nathan Goodyear on 10 Jan 14 - No Cached
  • Nathan Goodyear on 10 Jan 14
     
    Curcumin inhibits Telomerase activity in cancer cells.  
Nathan Goodyear

PLOS ONE: Telomerase Reverse Transcriptase Synergizes with Calorie Restriction to Incre... - 0 views

www.plosone.org/...journal.pone.0053760

calorie restriction calorie restriction health Longevity telomere telomeres

shared by Nathan Goodyear on 19 Feb 13 - No Cached
  • Nathan Goodyear on 19 Feb 13
     
    calorie restriction, though not malnutrition, is associated with longevity as determined by increased telomerase reverse transcriptase and a reduction in aged related diseases.  Granted this was a mouse model.
Nathan Goodyear

Cells | Free Full-Text | Functional Assessment of Pharmacological Telomerase Activators... - 0 views

www.mdpi.com/htm

TA-65 telomere Telomerase telomerase activator natural aging wellness health

shared by Nathan Goodyear on 16 May 16 - No Cached
  • Nathan Goodyear on 16 May 16
     
    Full study of previously posted abstract of TA-65 increase of telomere length in cell culture.
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

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

Estrogen reduces endothelial progenitor cell sen... [J Hypertens. 2005] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...16093915

Estrogen estradiol EPC endothelial progenitor cells aging

shared by Nathan Goodyear on 11 Jul 12 - No Cached
  • Nathan Goodyear on 11 Jul 12
     
    Estradiol inhibited EPC aging in this study.  What is interesting, is that this was accomplished through  telomerase activity and thus increasing telomere length.
Nathan Goodyear

Indole-3-carbinol downregulation of telomerase gene expression requires the inhibition ... - 0 views

carcin.oxfordjournals.org/...1315.full

indole-3-carbinol I3C breast cancer ER alpha estrogen cancer

shared by Nathan Goodyear on 18 Mar 13 - No Cached
  • Nathan Goodyear on 18 Mar 13
     
    Indole-3-carbinol (I3C) inhibits breast cancer cell growth through, in part, down regulation of ER alpha signaling.
Nathan Goodyear

A natural product telomerase activator as part of a health maintenance program: metabol... - 0 views

www.ncbi.nlm.nih.gov/...23808324

TA-65

shared by Nathan Goodyear on 16 May 16 - No Cached
  • Nathan Goodyear on 16 May 16
     
    TA-65 shown to improve fasting glucose, fasting insulin, total cholesterol, LDL, blood pressure, and homocysteine.
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