The telomerase activator TA-65 elongates short telomeres and increases health span of adult old mice without increasing cancer incidence
Bruno Bernardes de Jesus,Kerstin Schneeberger,Elsa Vera,Agueda M. Tejera,Calvin B. Harley,Maria A. Blasco +5 more
TLDR
TA‐65 dietary supplementation in female mice leads to an improvement of certain health‐span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.Abstract:
Summary Here, we show that a small-molecule activator of telomerase (TA-65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc + ⁄ ) MEFs). Importantly, TA-65 does not cause telomere elongation or rescue DNA damage in similarly treated telomerase-deficient G3 Terc ) ⁄ ) littermate MEFs. These results indicate that TA-65 treatment results in telomerase-dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA-65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA-65 is capable of increasing mouse telomerase reverse transcriptase levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.read more
Citations
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The Hallmarks of Aging
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.
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Telomerase Gene Therapy in Adult and Old Mice Delays Aging and Increases Longevity Without Increasing Cancer
Bruno Bernardes de Jesus,Elsa Vera,Kerstin Schneeberger,Agueda M. Tejera,Eduard Ayuso,Fatima Bosch,Maria A. Blasco +6 more
TL;DR: A proof‐of‐principle of a role of TERT in delaying physiological aging and extending longevity in normal mice through a telomerase‐based treatment is formed, and the feasibility of anti‐aging gene therapy is demonstrated.
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Axis of ageing: telomeres, p53 and mitochondria.
Ergun Sahin,Ronald A. DePinho +1 more
TL;DR: A molecular circuit that directly links DNA damage to compromised mitochondrial biogenesis and function via p53 may account for both organ decline and disease development associated with advanced age and could illuminate a path for the development of relevant therapeutics.
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Ageing and the telomere connection: An intimate relationship with inflammation.
Jingwen Zhang,Grishma Rane,Xiaoyun Dai,Muthu K. Shanmugam,Frank Arfuso,Ramar Perumal Samy,Mitchell K.P. Lai,Dennis Kappei,Alan Prem Kumar,Gautam Sethi +9 more
TL;DR: The intricate association between the various inflammatory molecules and telomeres that together contribute to the ageing process and related diseases are summarized.
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Stress, cell senescence and organismal ageing.
TL;DR: The role of telomere dysfunction and senescence during the ageing process as well as potential interventions, including pharmacological approaches like telomerase activators and senolytics, to counteract their detrimental effects in ageing and disease are focused on.
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