TERT

telomerase reverse transcriptase

Gene Information

Gene Symbol
TERT
Aliases
TRT, TP2, TCS1, hEST2, EST2
HGNC ID
HGNC:11730
NCBI Gene ID
7015
Ensembl Gene ID
ENSG00000164362
Gene Type
protein coding

Genomic Location

Chromosome
5
Assembly
GRCh38
Start Position
1,253,147
End Position
1,295,085
Number of Exons
16
Gene Length
41,939 bp

Overview

Telomerase repairs/elongates the telomeres and is crucial in cellular proliferation. TERT expression is sufficient to overcome cellular senescence in culture, but overexpression of TERT in mice does not extend longevity. Most human cell lines have low or insignificant levels of TERT while cancer cells often have high levels. TERT expression in primary human fibroblasts results in a linear increase in DNA methylation age with cell population doubling number, indicating that TERT may also play a role in regulating the epigenetic clock. Cardiac-specific Tert activation after myocardial infarction in adult mice results in attenuated cardiac dilation, improved ventricular function, smaller infarct scars and increased mouse survival. Tert expression in a mouse model of pulmonary fibrosis improved lung function and lowered inflammation and fibrosis in addition to lowering DNA damage, apoptosis and senescence. In humans, mutations in TERT have been linked to aplastic anaemia. As such, TERT appears to be an important player in cellular proliferation, even if its relation to human ageing remains obscure.

Research Papers

20 papers in databaseSearch for More Papers
#1
Score:
100%

cGAS-STING are responsible for premature aging of telomerase-deficient zebrafish.

EMBO J
2025
PMID: 40490553

Modification Effects

STING pathway activation; increased senescence, inflammation, and DNA damage response, p53 stabilization

Longevity Association

Delayed aging and increased healthspan/lifespan in telomerase-deficient zebrafish; mechanism: reduced senescence, inflammation, and DNA damage response

#2
Score:
90%

Circular RNA Telomerase Reverses Endothelial Senescence in Progeria.

Aging Cell
2025
PMID: 39988827

Modification Effects

TERT circular RNA expression; extended telomerase activity, increased telomere length

Longevity Association

Reversal of endothelial senescence in progeria; 3-fold reduction in beta-gal positive cells, improved cellular markers and functions in HGPS endothelial cells

#3
Score:
90%

New intranasal and injectable gene therapy for healthy life extension.

Proc Natl Acad Sci U S A
2022
PMID: 35537048

Modification Effects

Overexpression of TERT and FST proteins; telomere lengthening and mitochondrial structure preservation

Longevity Association

41.4% and 32.5% median lifespan extension in mice; improved glucose tolerance, physical performance, and prevention of age-related phenotypes

#4
Score:
90%

Gut-specific telomerase expression counteracts systemic aging in telomerase-deficient zebrafish.

Nat Aging
2023
PMID: 37142828

Modification Effects

Gut-specific telomerase expression; prevention of telomere shortening, rescue of premature aging, and restoration of tissue integrity

Longevity Association

40% lifespan extension in telomerase-deficient zebrafish; mechanism: telomere elongation, reduced gut senescence, and systemic beneficial impacts on distant organs

#5
Score:
90%

Modification of the telomerase gene with human regulatory sequences resets mouse telomeres to human length.

Nat Commun
2025
PMID: 39905075

Modification Effects

Humanized mTert gene (hmTert) with replaced non-coding sequences; repressed in adult tissues except gonads and thymus, mimics human TERT regulation

#6
Score:
90%

Genetic Engineering of Humanized Telomere Mice.

Bio Protoc
2025
PMID: 41000148

Modification Effects

Humanized telomerase gene (hmTert) replacement in mouse Tert locus; altered telomere length dynamics

#7
Score:
90%

Endothelial-specific telomerase inactivation causes telomere-independent cell senescence and multi-organ dysfunction characteristic of aging.

Aging Cell
2024
PMID: 38475941

Modification Effects

Tert knockout in endothelial cells; transcriptional changes, reduced mitochondrial content and function, increased dependence on glycolysis

Longevity Association

Multi-organ dysfunction, cognitive impairment, reduced muscle endurance, and metabolic changes; mechanism: telomere length-independent undermining of mitochondrial function, vascular senescence

#8
Score:
90%

Telomere shortening induces aging-associated phenotypes in hiPSC-derived neurons and astrocytes.

Biogerontology
2024
PMID: 37987889

Modification Effects

Telomere shortening via CRISPR/Cas9-mediated loss of telomerase function; increased cellular senescence, heightened inflammation, elevated DNA damage

Longevity Association

Induced aging-associated phenotypes in human neurons and astrocytes; mechanism: telomere shortening, increased cellular senescence and DNA damage

#9
Score:
90%

Lack of telomerase reduces cancer incidence and increases lifespan of zebrafish tp53(M214K) mutants.

Sci Rep
2024
PMID: 38443436

Modification Effects

tp53 M214K mutation; altered p53 response, telomerase deficiency (tert -/-); impaired cell proliferation and increased DNA damage

Longevity Association

Increased lifespan in zebrafish tp53(M214K) mutants with telomerase deficiency; 2-fold reduced cancer incidence; mechanism: reduced telomere-driven DNA damage and apoptosis

#10
Score:
90%

Telomerase is required for zebrafish lifespan.

PLoS Genet
2013
PMID: 23349637

Modification Effects

Telomerase deficiency (tert(-/-)); impaired cell proliferation, accumulation of DNA damage markers, p53 response, and early apoptosis

Longevity Association

Premature death in zebrafish; degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopaenia; mechanism: telomere shortening, telomere instability, and p53-mediated apoptosis

#11
Score:
90%

A novel autosomal recessive TERT T1129P mutation in a dyskeratosis congenita family leads to cellular senescence and loss of CD34+ hematopoietic stem cells not reversible by mTOR-inhibition.

Aging (Albany NY)
2015
PMID: 26546739

Modification Effects

TERT T1129P mutation; impaired telomerase activity, reduced CD34+ hematopoietic stem cells

Longevity Association

Premature cellular senescence, bone marrow failure; mTOR inhibition partially rescues fibroblast survival but not HSC function in mice

#12
Score:
80%

Development of a Short Telomere Zebrafish Model for Accelerated Aging Research and Antiaging Drug Screening.

Aging Cell
2025
PMID: 39921881

Modification Effects

Shortened telomeres; reduced telomerase expression and activity; increased cellular senescence and apoptosis

Longevity Association

Premature aging phenotype in zebrafish; resveratrol improves telomere maintenance, potential for increased lifespan

#13
Score:
80%

TERT activation targets DNA methylation and multiple aging hallmarks.

Cell
2024
PMID: 38908367

Modification Effects

TERT activation via MEK/ERK/AP-1 cascade; increased telomere synthesis, DNMT3B-mediated promoter hypermethylation

Longevity Association

Reduced cellular senescence, inflammatory cytokines, and neuroinflammation; increased adult neurogenesis, preserved cognitive function in mice; potential for mitigating multiple aging hallmarks

#14
Score:
80%

Genetic regulation of TERT splicing affects cancer risk by altering cellular longevity and replicative potential.

Nat Commun
2025
PMID: 39956830

Modification Effects

VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.5-66.5 repeats) and rs10069690-T allele; alternative splicing and nonsense-mediated decay affecting TERT expression

Longevity Association

Association with age-related telomere shortening and cancer risk; regulation of cellular longevity and replicative potential through TERT splicing in humans

#15
Score:
80%

Mechanism of age-related accumulation of mitochondrial DNA mutations in human blood.

bioRxiv
2025
PMID: 40501828

Modification Effects

Mitochondrial DNA mutations accumulate with age; increased mtDNA heteroplasmy

Longevity Association

Association with aging and clonal hematopoiesis in human blood; mechanism involves mtDNA replication errors and clonal expansion

#16
Score:
80%

Caloric Restriction and Telomere Preservation in TERT Knockout Adipocyte Progenitors Does Not Rescue Mice From Metabolic Dysfunction due to a TERT Function in Adipocyte Mitochondria.

Aging Cell
2025
PMID: 39932851

Modification Effects

TERT knockout; decreased mitochondrial oxidative metabolism, reliance on glycolysis in adipocytes

Longevity Association

Metabolic dysfunction, reduced cold tolerance, and abnormal thermogenesis in mice; TERT's non-canonical function in adipocyte mitochondria affects aging

#17
Score:
80%

Balance between senescence and apoptosis is regulated by telomere damage-induced association between p16 and caspase-3.

J Biol Chem
2018
PMID: 29748384

Modification Effects

p16 mutation with impaired caspase-3 association; altered senescence and apoptosis regulation

Longevity Association

Accelerated aging in SphK2-deficient mice; mechanism: increased telomere damage, senescence, and telomerase instability

#18
Score:
80%

Relative Leukocyte Telomere Length and Genetic Variants in Telomere-Related Genes and Serum Levels Role in Age-Related Macular Degeneration.

Cells
2022
PMID: 36497103

Modification Effects

Genetic variants in TRF1 (rs10107605, rs1545827) and TRF2 (rs251796); altered telomere length and TERF1 serum levels

Longevity Association

Association with age-related macular degeneration (AMD) development in humans; telomere shortening and genetic variants influence AMD risk

#19
Score:
80%

METTL3-mediated modification of SIRT1 m6A methylation protects osteoblasts from TBHP-induced senescence and promotes osteoblast proliferation.

Chem Biol Interact
2025
PMID: 40716628

Modification Effects

METTL3-mediated m6A methylation of SIRT1 mRNA; enhanced SIRT1 mRNA stability and inhibited osteoblast senescence

Longevity Association

Increased bone mass in aged mice; mechanism: METTL3-m6A-SIRT1-YTHDF2 axis inhibits osteoblast senescence and promotes proliferation

#20
Score:
80%

Telomere length and aging-related outcomes in humans: A Mendelian randomization study in 261,000 older participants.

Aging Cell
2019
PMID: 31444995

Longevity Association

Lowered risk of coronary heart disease (OR = 0.95); raised risk of cancer (OR = 1.11) with longer telomere length in humans

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