Role of Telomeres and Telomerase in Aging and Cancer
Open accessAbstract
Telomeres progressively shorten throughout life. A hallmark of advanced malignancies is the ability for continuous cell divisions that almost universally correlates with the stabilization of telomere length by the reactivation of telomerase. The repression of telomerase and shorter telomeres in humans may have evolved, in part, as an anticancer protection mechanism. Although there is still much we do not understand about the regulation of telomerase, it remains a very attractive and novel target for cancer therapeutics. This review focuses on the current state of advances in the telomerase area, identifies outstanding questions, and addresses areas and methods that need refinement. Significance: Despite many recent advances, telomerase remains a challenging target for cancer therapy. There are few telomerase-directed therapies, and many of the assays used to measure telomeres and telomerase have serious limitations. This review provides an overview of the current state of the field and how recent advances could affect future research and treatment approaches. Cancer Discov; 6(6); 584–93. ©2016 AACR.
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The pathogenicity of telomere shortening in ageing is an antagonistic pleiotropic effect of a trait selected for early benefits such as limiting proliferation and tumor formation.
“The pathogenicity of telomere shortening in ageing is an antagonistic pleiotropic effect of a trait that must have been selected for its early benefits such as limiting unrestrainted proliferation and hence tumor formation14.”
From The central role of DNA damage in the ageing process (2021) · cites this paper as [14]
TERT silencing downregulates telomerase activity in human somatic cells.
“TERT silencing downregulates telomerase activity in human somatic cells (reviewed in REF. 22).”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [22]
Most malignancies aim to maintain a sufficient length of telomeres in order to enhance their duplication rate and survival.
“Notably, most malignancies aim to maintain a sufficient length of telomeres in order to enhance their duplication rate and survival [ 266 ].”
From Targeting PP2A in cancer: an underrated option (2025) · cites this paper as [266]
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Regulation of Telomerase Alternative Splicing: A Target for Chemotherapy
Wong, M. S., Chen, L., Foster, C., Kainthla, R., Shay, J. W., & Wright, W. E. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.011 · Cited by 59 · see citing works
Self-citationWu, R. A., Dagdas, Y. S., Yılmaz, S. T., Yıldız, A., & Collins, K. (2015) · eLife · doi:10.7554/elife.08363 · Cited by 39 · see citing works
Regulation of human telomerase splicing by RNA:RNA pairing
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Self-citationPerifosine as a potential novel anti-telomerase therapy
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Self-citationImplications of Mapping the Human Telomerase Gene (hTERT) as the Most Distal Gene on Chromosome 5p
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Self-citationResponse : Telomeres, Telomerase, and Cancer
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Self-citationTelomerase activity in human germline and embryonic tissues and cells
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Self-citation
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Cellular Senescence: Aging, Cancer, and Injury
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“Telomeres as anticancer targets Given that most tumors (85–90%) present telomerase activity, whereas telomerase is absent in most normal tissues, or is strictly regulated in transient-amplifying stem cells, inhibition of telomerase is an attractive target for cancer therapy (Kim et al., 1994; Shay, 2016).”
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The Impact of Sunlight on Skin Aging
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Targeting PP2A in cancer: an underrated option
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- Authors
- Shay, J. W.
- Affiliations
- King Abdulaziz University (SA)
- Corresponding author
- Shay, Jerry W.
- ORCID
- Shay, Jerry W.
- Venue
- Cancer Discovery
- Published
- 2016-06-01
- Volume
- 6
- Issue
- 6
- Pages
- 584-593
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC4893918
- OpenAlex
- W2321647501
- Cited by
- 668
- References
- 98
- Citations by year
- 2026: 35 · 2025: 69 · 2024: 72 · 2023: 60 · 2022: 69 · 2021: 107 · 2020: 76 · 2019: 66 · 2018: 52 · 2017: 44 · 2016: 13 · 2015: 2 · 2012: 1
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P50CA70907)
- Southland Financial Foundation in Geriatrics Research (RO1 AG001228)
- NIH (C06 RR30414)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- telomeres, telomerase, aging, cancer, telomere shortening, telomerase reactivation, telomere length measurement
- MeSH terms
- Aging, Animals, Cell Transformation, Neoplastic, Humans, Neoplasms, Telomere, Apoptosis, Telomerase, Cell Proliferation, Telomere Homeostasis, Telomere Shortening
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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