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The telomerase activator TA‐65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence
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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.
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“A natural plant compound named TA-65 has been reported to boost telomerase activity and lengthen telomeres in mice189.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [189]
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“Accordingly, natural or synthetic compounds that induce TERT expression have been shown to promote cellular survival and metabolic fitness.17–19”
From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [17]
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“Moreover, normal physiological aging can be delayed without increasing the incidence of cancer in adult wild-type mice by pharmacological activation or systemic viral transduction of telomerase (Bernardes de Jesus et al., 2012; de Jesus et al., 2011).”
From The Hallmarks of Aging (2013) · cites this paper as de Jesus et al., 2011
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“Telomerase activation is envisioned as a potential strategy to rejuvenate tissues and to treat diseases characterized by premature telomere shortening (de Jesus et al, 2011; Jaskelioff et al, 2011).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as de Jesus et al, 2011
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Metadata
- Authors
- de Jesus, B. B., Schneeberger, K., Vera, E., Tejera, A., Harley, C. B., & Blasco, M. A.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2011-04-14
- Volume
- 10
- Issue
- 4
- Pages
- 604-621
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3627294
- OpenAlex
- W2102172732
- Cited by
- 348
- References
- 85
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 23 · 2023: 30 · 2022: 31 · 2021: 34 · 2020: 31 · 2019: 18 · 2018: 21 · 2017: 25 · 2016: 18 · 2015: 21 · 2014: 15 · 2013: 21 · 2012: 21
- FWCI
- 12.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- European Commission
- Ministerio de Ciencia e Innovación
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- telomerase activators, telomere length, telomerase reverse transcriptase, Astragalus membranaceus, DNA damage, healthspan, dietary supplementation, cancer incidence, glucose tolerance, osteoporosis, skin aging
- MeSH terms
- Animals, Diet, DNA Damage, Embryo, Mammalian, Female, Fibroblasts, Mice, Inbred C57BL, Neoplasms, RNA, Anticarcinogenic Agents, Telomere, Telomerase, Astragalus propinquus, Mice
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