Verified 2026-05-07 against Bodnar 1998, Bernardes de Jesus 2012, Nguyen 2018, and Vogan 2016 PDFs. Material correction: the Cajal body section previously stated TCAB1-deficient cells have reduced TERT recruitment to telomeres — corrected to reflect Vogan 2016’s actual finding that TCAB1 and Cajal bodies are not essential for telomere maintenance. Nguyen 2018 structural resolution corrected: 7.7 Å / 8.2 Å (per lobe) + 10.2 Å (overall holoenzyme); not “~7–9 Å.” TPP1 TEL patch citation PMIDs corrected (seeder PMIDs were wrong — correct papers: Nandakumar 2012 doi:10.1038/nature11648 and Schmidt 2014 doi:10.7554/eLife.03563). Unverified against full text: Greider 1985, Cohen 2007, Heaphy 2011 (all permanently not_oa).

Telomerase pathway

The telomerase pathway is the ribonucleoprotein enzyme system that extends telomeric DNA at chromosome ends, counteracting the replicative attrition imposed by the end-replication problem. Its catalytic core — the TERT reverse transcriptase complexed with the TERC RNA template — is tightly regulated across the human lifespan: constitutively active in germline, embryo, and a restricted set of adult stem cells; epigenetically silenced in most post-mitotic and replicative somatic cells; and reactivated in ~85% of human cancers. The progressive extinction of telomerase activity in adult somatic stem cells is the primary molecular driver of the telomere-attrition hallmark, making this pathway the most mechanistically direct target of that hallmark.

Naming note: This page covers the telomerase pathway — holoenzyme assembly, recruitment, reaction cycle, and regulation. Molecular detail for the TERT catalytic subunit lives at tert (verified). Companion stubs seeded in the same batch: terc, dkc1, shelterin, tpp1, tin2, trf1, trf2, pot1.

Pathway overview

Telomerase acts in four coordinated stages:

Holoenzyme assembly in Cajal bodies — TERT + TERC + H/ACA RNP scaffold (DKC1, NHP2, NOP10, GAR1) + TCAB1 assemble into the functional holoenzyme
Recruitment to telomeres — shelterin subunit tpp1 engages TERT’s C-terminal extension (CTE) at its TEL patch domain, tethering telomerase to the G-overhang
Telomere elongation — TERT catalyzes processive TTAGGG repeat synthesis using the TERC template
Translocation and re-extension — after each repeat, telomerase translocates and re-aligns the template for the next cycle

Reactome organizes this under R-HSA-157579 (Telomere Maintenance), which contains three child reactions: R-HSA-180786 (Extension of Telomeres), R-HSA-171306 (Packaging of Telomere Ends), and R-HSA-9006821 (Alternative Lengthening of Telomeres).

Holoenzyme composition

The telomerase holoenzyme was biochemically defined by Cohen et al. purifying catalytically active enzyme from immortal human cells ¹:

Subunit	Gene	Role in holoenzyme
TERT	TERT	Catalytic reverse transcriptase; synthesizes TTAGGG repeats
TERC	TERC (ncRNA, 451 nt)	RNA template; provides 3’-AAUCCC-5’ template sequence; CR4/CR5 domain binds TERT CTE
Dyskerin	DKC1	H/ACA RNP pseudouridine synthase; stabilizes TERC; loss-of-function → dyskeratosis congenita
NHP2	NHP2	H/ACA RNP structural scaffold
NOP10	NOP10	H/ACA RNP structural scaffold
GAR1	GAR1	H/ACA RNP; contacts RNA substrate during catalysis
TCAB1	TCAB1 (WRAP53)	Cajal body localization signal receptor; required for holoenzyme trafficking to Cajal bodies before telomere association

Cohen et al. used affinity purification of FLAG-tagged TERT followed by mass spectrometry to establish this composition ¹. The finding that dyskerin (DKC1) is an obligate holoenzyme component explained why X-linked DKC1 loss-of-function mutations cause dyskeratosis congenita (DC) — a telomere-maintenance disease — despite DKC1 being a pseudouridine synthase: its primary role in telomerase is TERC stabilization, not catalysis. needs-replication — the full stoichiometry of the holoenzyme (e.g., TERT:TERC copy ratio) remains debated.

The 3D architecture was resolved by Nguyen et al. using cryo-EM of the substrate-bound human holoenzyme ². The catalytic core and H/ACA lobes were reconstructed separately by focused classification at 7.7 Å and 8.2 Å resolution respectively; the overall holoenzyme reconstruction was obtained at 10.2 Å resolution. The holoenzyme has a bilobal architecture: one lobe contains the catalytic core (TERT ring encircling hTR with the template/pseudoknot t/PK and CR4/CR5 domains), and the other lobe contains the H/ACA RNP components (two sets of H/ACA heterotetramers comprising dyskerin/NOP10/NHP2/GAR1 and one TCAB1). The t/PK and CR4/CR5 hTR domains wrap around TERT to form the catalytic core, with P6.1 hairpin inserting into the TRBD-CTE interface — critical for TERT association with hTR and catalytic activity. The H/ACA RNP lobe is spatially separated from the catalytic lobe and bridged only by flexible hTR stems, consistent with its RNA stabilization role rather than direct catalysis.

Cajal body assembly and TCAB1

Newly synthesized TERC accumulates in Cajal bodies (CBs), nuclear organelles where RNA processing occurs. TCAB1 (also known as WRAP53/WDR79) recognizes a CAB box motif in TERC’s 3’ region and is required for holoenzyme localization to CBs ³. TCAB1 KO abolishes CB localization of hTR telomerase and redistributes the RNP to the nucleoplasm.

However, Cajal body localization is not essential for telomere maintenance. Vogan et al. demonstrated that TCAB1 KO in both HCT116 cancer cells and human embryonic stem cells (hESCs) did not prevent stable telomere length homeostasis — TCAB1 KO hESC lines showed gradual telomere shortening followed by stable maintenance rather than progressive attrition, and neither TCAB1 KO nor Coilin KO detectably impaired telomerase catalytic activity in cell extract ³. Telomere maintenance by minimized hTR telomerase (hTRmin, which lacks H/ACA RNP biogenesis requirements) was likewise unaffected by TCAB1 KO. The prior model of CB association as a strict rate-limiting checkpoint is therefore not supported — CB transit facilitates efficient assembly but is dispensable for telomere maintenance in cells with adequate TERT expression.

The Cajal body association model remains relevant as an efficiency mechanism in stem cells with low endogenous TERT levels, where TCAB1-mediated concentration in CBs may increase productive TERT-TERC encounter frequency. needs-replication — the degree to which CB association is limiting in primary adult stem cells (not overexpression or cancer-cell contexts) has not been directly tested.

Shelterin-mediated recruitment

Telomerase does not bind naked telomeric DNA. Its recruitment is mediated by the shelterin complex — a six-protein cap on chromosome ends comprising trf1, trf2, pot1, tpp1, tin2, and RAP1. The critical interface is tpp1 (encoded by ACD):

TPP1’s TEL patch domain (a positionally conserved surface on the OB fold) binds directly to the TERT CTE domain
TPP1-TIN2 form a stable sub-platform anchored to the double-stranded telomeric DNA via TRF1 and TRF2
POT1 binds the single-stranded G-overhang, and POT1-TPP1 interaction additionally stimulates telomerase processivity

Disruption of the TPP1 TEL patch (specific surface mutations) abolishes telomerase recruitment without disrupting shelterin integrity, establishing TPP1 as the primary telomerase-recruitment factor ⁴⁵. The TEL patch on TPP1’s OB fold mediates both telomerase recruitment and processivity — POT1-TPP1 stimulation of processivity is structurally separable from recruitment ⁴.

The combined POT1-TPP1 module also increases the processivity of telomere elongation: telomerase switches from distributive (one repeat per telomere binding event) to processive (multiple sequential repeats) when TPP1 and POT1 are present. This translates biochemical activity into biologically meaningful telomere extension per S-phase.

Elongation reaction cycle

Telomerase catalysis follows an unusual mechanism for a processive polymerase ⁶:

Primer binding — the 3’ single-stranded G-overhang docks in the TERT TEN domain anchor site
Template alignment — the TERC template region (3’-AAUCCC-5’) pairs with the 3’ end of the primer; only ~5–6 template nucleotides are used per cycle
Nucleotide addition — TERT’s RT active site (YADD motif in RT domain) catalyzes dNTP addition; one TTAGGG repeat is synthesized by copying the template 3’→5’
Translocation — after completing one repeat, the newly synthesized DNA and TERC template must translocate relative to each other so the 3’ end of the new repeat realigns with the 5’ end of the template — the rate-limiting step for processivity
Re-extension — template re-pairs and a new repeat cycle begins; human telomerase can add 3–8 repeats per binding event under optimal conditions

The translocation step is mechanistically distinct from canonical DNA polymerase processivity because the template is short and repeated. The TERT TEN domain and TERC pseudoknot both contribute to holding the DNA-RNA duplex during translocation. Failure to translocate results in distributive behavior (one repeat per binding event), which is insufficient for telomere maintenance in highly proliferative stem cells.

Regulation of telomerase activity

Transcriptional silencing of TERT in somatic cells

TERT expression is the primary regulatory bottleneck: TERC is constitutively expressed in most tissues; DKC1 and the H/ACA RNP components are housekeeping genes. Whether telomerase is active therefore depends almost entirely on whether TERT is transcribed. In adult somatic cells, TERT is epigenetically silenced by:

CpG methylation of the TERT core promoter (bimodal methylation correlated with silencing)
Polycomb repressive complex 2 (PRC2) / H3K27me3 deposition over the TERT locus
CTCF / mSin3A-HDAC co-repressor binding at E-box motifs in the promoter

Germline and early embryonic cells maintain TERT expression via MYC/MAX heterodimers and active chromatin at the promoter. Adult stem cells (HSCs, intestinal crypt cells, hair follicle bulge cells) express low but detectable TERT, sufficient for partial telomere maintenance but not full erosion arrest across a lifetime. unsourced — the specific CpG methylation sites and their quantitative correlation with TERT silencing are not catalogued here; see ENCODE WGBS tracks for TERT locus.

This silencing pattern is the evolutionary compromise that limits cancer risk in long-lived organisms (by preventing the constitutive replicative immortality that telomerase would confer) at the cost of progressive telomere erosion in somatic stem cells.

Cancer reactivation

~85% of human cancers reactivate TERT expression. The dominant mechanism is recurrent gain-of-function point mutations in the TERT core promoter — C228T and C250T — which create de novo ETS transcription factor binding sites (GGAA) at −124 and −146 bp upstream of the ATG [^horn2013]. This is distinct from TERT gene amplification (a minority mechanism). TERT promoter mutations are among the most common non-coding mutations in cancer and are enriched in melanoma (~70%), glioblastoma (~60–80%), bladder cancer, and hepatocellular carcinoma. needs-replication — pan-cancer frequency estimates vary by tissue and study cohort.

Post-translational regulation

TERT activity is modulated by phosphorylation-dependent nuclear trafficking: AKT (Ser-227) promotes nuclear import; Src-family kinases (Tyr-707) promote export; Ser-457 marks for proteasomal degradation. See tert for full details. pi3k-akt-pathway therefore positively regulates telomere maintenance beyond its canonical growth-factor outputs.

Cell-cycle gating

Telomerase recruitment to telomeres is S-phase-restricted in human cells. TPP1 phosphorylation by CDK2 during S-phase may gate telomerase access [^gap_cdk2]. unsourced — CDK2-TPP1 phosphorylation gating is described in the literature (see Lee et al. 2015, PMID 26148048) but has not been verified to citation-standard on this page.

Alternative Lengthening of Telomeres (ALT)

~15% of cancers and a small number of telomerase-negative normal cells maintain telomeres through ALT — a recombination-based mechanism that does not require TERT. Key features ⁷:

ALT is associated with loss-of-function mutations in ATRX (alpha-thalassemia/mental retardation X-linked) and DAXX (death domain-associated protein), chromatin remodelers that normally suppress recombination at telomeres
ALT tumors show ultralong, heterogeneous telomere lengths; extrachromosomal telomeric circles (ECTCs/t-circles); and telomere sister-chromatid exchange (T-SCE) — all signatures of recombination-mediated elongation
ALT is particularly prevalent in soft tissue sarcomas, gliomas (grade 2/3), and osteosarcomas
ATRX/DAXX loss is thought to permit HR-mediated copy-number transfer between telomeric repeats, effectively using other telomeres or ECTCs as templates

Heaphy et al. established the ATRX/DAXX loss → ALT link by sequencing a large panel of pancreatic neuroendocrine tumors and demonstrating co-occurrence of ATRX mutations with ALT signatures ⁷. The ALT mechanism remains incompletely characterized — the enzymatic machinery (which Holliday junction resolvases, which strand-invasion factors) has not been fully resolved. no-mechanism

ALT and telomerase are largely mutually exclusive in cancers, reflecting two independent solutions to the same selection pressure (replicative immortality). For normal aging biology, ALT is primarily relevant as a background against which telomerase-specific interventions must be interpreted.

Role in aging

End-replication problem and somatic stem cell attrition

DNA polymerase cannot replicate the 3’ end of the lagging strand, resulting in progressive telomere shortening with each cell division — the end-replication problem. In telomerase-negative somatic cells, this produces 50–200 bp loss per division [^greider1985_context]. Cells with critically short telomeres (below ~5–8 kb in humans) activate a DNA damage response (ATM/ATR at uncapped telomere ends) that drives irreversible cellular-senescence or apoptosis.

The foundational demonstration that TERT introduction is sufficient to bypass this: Bodnar et al. introduced hTRT (hTERT) cDNA into normal human RPE retinal pigment epithelial cells (RPE-340, transfected at PD 37) and BJ foreskin fibroblasts (transfected at PD 44 or PD 58 depending on construct), maintaining telomere length and extending replicative capacity by 20–36 population doublings beyond controls ⁸, establishing that somatic cell replicative senescence is telomere-length-dependent and TERT-reversible.

Critically, telomere attrition is not uniform across tissues. Cells with the highest replicative burden — hematopoietic stem cells, intestinal crypt stem cells, hair follicle bulge cells, airway basal cells — experience the fastest attrition. This predicts that tissues dependent on high-turnover stem cell pools will exhibit the earliest and most severe age-related dysfunction, which matches the clinical phenotype of telomere biology disorders (bone marrow failure, mucosal atrophy, pulmonary fibrosis).

Lifespan extension by TERT restoration in mice

Bernardes de Jesus et al. delivered AAV9-mTert by single IV injection to >95% C57BL/6 background mice at 1 or 2 years of age, extending median lifespan by +24% and +13% respectively, without increasing cancer incidence (p=0.87) ⁹. This is the strongest single result linking telomere maintenance restoration to mammalian lifespan extension via a clinically tractable delivery modality. Full mouse-to-human extrapolation caveats are detailed on tert and telomere-attrition (verified against primary source PDF).

Dimension	Status
Pathway conserved in humans?	yes — TERT/TERC/shelterin axis conserved; holoenzyme composition confirmed in human cells
Phenotype conserved in humans?	partial — end-replication problem and senescence are universal; mouse telomeres are ~5–10x longer than human, so the starting state differs substantially
Replicated in humans?	no lifespan data; in-vitro senescence rescue replicated across multiple human cell types

Pharmacology and therapeutic landscape

Direction	Class	Example agents	Target	Aging-context tier
Inhibition (anti-cancer)	Oligonucleotide template antagonist	Imetelstat (GRN163L)	TERC template region	Tier 1 (FDA-approved 2024 for MDS)
Inhibition (anti-cancer)	Small-molecule TERT inhibitor	BIBR1532	TERT RT active site	Tier 3 (preclinical only)
Activation (pro-longevity)	Putative TERT transcriptional activator	TA-65 (cycloastragenol), GRN510	TERT promoter (mechanism disputed)	Tier 3–4 (supplement; no RCT)
Delivery (pro-longevity)	AAV gene therapy	AAV9-mTert (Bernardes 2012)	TERT expression restoration	Tier 3–4 (preclinical; human translation blocked)

Druggability-tier rationale (aging context): The only clinically approved telomerase-targeting drug (imetelstat) works by inhibiting telomerase in a cancer indication — the opposite of what aging applications require. For the aging-activation direction, the most advanced approach (AAV-TERT) is preclinical-only; the most clinically available compound (TA-65) lacks a powered RCT and has disputed mechanism. No validated clinical-grade probe exists for telomerase activation in humans. The pathway therefore sits at tier 2 in aging-context (tier 1 tools exist, but only for the oncology/inhibition direction; activation direction is tier 3–4). dose-response-unclear — optimal dose and delivery modality for telomerase activation without oncogenic risk in humans is not established.

Connection to other aging pathways and hallmarks

telomere-attrition — the downstream hallmark; this pathway is its primary molecular cause. Telomere length is the integrating biomarker; rate of attrition is determined by TERT activity levels + replicative history.
cellular-senescence — telomere-driven DDR (ATM/ATR at uncapped ends) is a major inducer of the senescent state; senescent cells secrete SASP which propagates chronic-inflammation and tissue dysfunction.
dna-damage-response — uncapped telomeres are recognized as double-strand breaks; ATM/ATR signaling is activated; p53 and p21 enforce senescence or apoptosis. p53-pathway transcriptionally represses TERT (negative feedback loop reinforcing senescence once initiated). unsourced — the p53→TERT transcriptional repression mechanism is described in the literature but not yet cited on this page.
stem-cell-exhaustion — high-turnover stem cell compartments (HSC, intestinal crypt, hair follicle bulge) accumulate the most telomere attrition; late-generation Tert-knockout mice (G3/G4) recapitulate stem-cell exhaustion phenotypes before other hallmarks become overt.
pi3k-akt-pathway — AKT phosphorylates TERT Ser-227, promoting nuclear localization and telomerase activity; the growth-factor → AKT → TERT axis links nutrient/growth-factor sensing to telomere maintenance.
OncoSENS — telomere-driven replicative immortality is a core oncogenic event in the OncoSENS SENS category; the cancer/aging tradeoff of TERT silencing maps directly onto this category.

Limitations and gaps

Human lifespan evidence is absent. All longevity-extension results (Bernardes de Jesus 2012, Tomás-Loba 2008) are from mice. The cancer-risk constraint is far more severe in humans; no equivalent of the Sp53/Sp16/SArf cancer-resistant background exists clinically. needs-human-replication
KEGG does not have a standalone human telomerase pathway entry. Telomerase components appear embedded in hsa04218 (Cellular senescence) and cancer-related disease maps. The kegg field is null. needs-canonical-id
WikiPathways entry not confirmed. No curated WikiPathways telomerase pathway ID was found during seeding. needs-canonical-id
Cryo-EM structural claims are now verified. Nguyen 2018 PDF downloaded and verified 2026-05-07 — structural claims in the body corrected (resolution 7.7/8.2 Å per lobe; 10.2 Å overall).
TPP1 TEL patch residue contacts are now cited. Added ⁴ (doi:10.1038/nature11648) and ⁵ (doi:10.7554/eLife.03563). Note: the seeder PMIDs (25030370, 22037700) were WRONG — they mapped to unrelated papers. Correct PMIDs are 23103865 (Nandakumar 2012) and 25271372 (Schmidt 2014). Neither PDF is verified against local copy; the footnotes are from Crossref/PubMed metadata. no-fulltext-access
ALT mechanism is incomplete. The full enzymatic machinery enabling recombination-based telomere elongation (HR factors, resolvases) has not been resolved. no-mechanism
Non-canonical TERT functions are not covered here. TERT has reported non-telomeric roles (Wnt/β-catenin co-activation, NF-κB co-regulation, mitochondrial protection). These live on tert and are outside scope of this pathway page; they may constitute separate pathway entries when better characterized. no-mechanism

Cross-references

tert (verified-partial) — catalytic subunit; domain architecture, regulation, therapeutic landscape
terc (implicit stub) — obligate RNA template subunit
dkc1 (implicit stub) — H/ACA RNP dyskerin; DKC1 mutations → dyskeratosis congenita
tcab1 (implicit stub) — Cajal body targeting; WRAP53
shelterin (implicit stub) — telomere-capping complex; TPP1 recruits telomerase
tpp1 (implicit stub) — TEL patch domain; direct TERT CTE interface
tin2 (implicit stub) — TIN2 anchors TPP1-TRF1/TRF2 platform
trf1 (implicit stub) — double-stranded telomere binder; TRF1 loss → telomere fragility
trf2 (implicit stub) — double-stranded telomere binder; TRF2 loss → end-joining catastrophe
pot1 (implicit stub) — single-stranded G-overhang binder; POT1-TPP1 stimulates processivity
telomere-attrition — downstream hallmark
cellular-senescence — downstream process; telomere-uncapping DDR induces senescence
dna-damage-response — activated by uncapped telomeres; ATM/ATR → p53/p21 → senescence
p53-pathway — negative regulator of TERT transcription; feedback loop reinforcing senescence
pi3k-akt-pathway — AKT phosphorylates TERT Ser-227, promoting nuclear TERT
stem-cell-exhaustion — late-generation Tert-KO mice reproduce stem-cell exhaustion phenotypes
sens-damage-categories — OncoSENS category; telomere-immortality cancer/aging tradeoff

Footnotes

doi:10.1126/science.1138596 · Cohen SB, Graham ME, Lovrecz GO, Bache N, Robinson PJ, Reddel RR · in-vitro · Science 2007 · 315(5820):1850–1853 · model: human immortal cell lines (affinity-purified FLAG-TERT) · defined holoenzyme protein composition by mass spectrometry; established DKC1/NHP2/NOP10/GAR1/TCAB1 as obligate components; 657 citations · archive: not_oa (no local PDF) no-fulltext-access ↩ ↩²
doi:10.1038/s41586-018-0062-x · Nguyen THD, Tam J, Wu RA, Greber BJ, Toso D, Nogales E, Collins K · cryo-EM structural · Nature 2018 · 557(7704):190–195 · model: human telomerase holoenzyme reconstituted in HEK 293T cells (substrate-bound, T14AG3 DNA); 10 protein subunits total (1 TERT, 2 sets of 4 H/ACA proteins, 1 TCAB1) · bilobal architecture; catalytic core at 7.7 Å, H/ACA lobe at 8.2 Å, overall holoenzyme at 10.2 Å; hTR wraps around TERT with t/PK and CR4/CR5 domains flanking active site; H/ACA lobe bridged to catalytic core by flexible hTR stems; 225 citations · archive: local PDF available (downloaded 2026-05-07 via PMC) ↩
doi:10.7554/eLife.18221 · Vogan JM, Zhang X, Youmans DT, Regalado SG, Johnson JZ, Hockemeyer D, Collins K · in-vitro/cell-biology · eLife 2016 · 5:e18221 · model: human HCT116 colon carcinoma cells and hESC line WIBR#3; TCAB1 KO, Coilin KO, and TERT KO via Cas9; minimized hTR (hTRmin) reconstitution · KEY FINDINGS: (1) hTRmin telomerase lacking H/ACA RNP biogenesis signals assembles active enzyme and maintains telomeres when TERT is overexpressed; (2) TCAB1 KO abolished CB localization of telomerase but did NOT prevent stable telomere length maintenance in either HCT116 or hESC lines — gradual shortening followed by homeostasis in hESC TCAB1 KO, no effect in HCT116 TCAB1 KO; (3) Coilin KO also did not impair telomere maintenance; conclusion: Cajal body localization is not essential for telomere maintenance, though it may enhance efficiency at low TERT levels · archive: local PDF available (downloaded 2026-05-07 via PMC) ↩ ↩²
doi:10.1038/nature11648 · Nandakumar J et al. · Nature 2012 · 492:285–289 · model: human cells; biochemical + mutational analysis of TPP1 OB fold · identified the TEL patch — a positionally conserved surface on the TPP1 OB fold — as the direct interface mediating both telomerase recruitment to telomeres and processivity stimulation; TEL patch mutations abolish telomerase recruitment without disrupting shelterin assembly or POT1 binding · archive: not_oa locally (not checked) no-fulltext-access ↩ ↩² ↩³
doi:10.7554/eLife.03563 · Schmidt JC et al. · eLife 2014 · 3:e03563 · model: human cells; TERT domain mutational analysis · identified TERT CTE (C-terminal extension) residues necessary for telomerase recruitment to telomeres; established the TPP1 TEL patch — TERT CTE interface as the key telomerase-recruitment interaction in human cells · archive: OA (eLife); not checked locally ↩ ↩²
doi:10.1126/science.276.5312.561 · Lingner J, Hughes TR, Shevchenko A, Mann M, Lundblad V, Cech TR · in-vitro · Science 1997 · 276(5312):561–567 · model: Euplotes aediculatus (ciliate) + S. cerevisiae EST2 · purified telomerase; identified the catalytic subunit by reverse transcriptase motif conservation; 982 citations · archive: download failed (OA URL HTML-only; infoscience mirror) no-fulltext-access ↩
doi:10.1126/science.1207313 · Heaphy CM, de Wilde RF, Jiao Y et al. · genomic/tumor sequencing · Science 2011 · 333(6041):425 · model: human pancreatic neuroendocrine tumors · identified recurrent ATRX and DAXX loss-of-function mutations associated with ALT signatures (ultralong telomeres, ECTCs, T-SCE); 1035 citations · archive: not_oa (no local PDF) no-fulltext-access ↩ ↩²
doi:10.1126/science.279.5349.349 · Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE · in-vitro · Science 1998 · 279(5349):349–352 · model: normal human RPE-340 retinal pigment epithelial cells (transfected at PD 37 with MPSV-hTRT) and BJ foreskin fibroblasts (transfected at PD 58 with MPSV-hTRT or PD 44 with pZeoSV-hTRT); hTRT (hTERT) cDNA overexpression · telomere length maintained and elongated in hTRT+ clones (RPE: +3.7 kbp; BJ MPSV: +7.1 kbp); RPE hTRT+ exceeded hTRT- mean lifespan by ~20 PD (P<10^-24, Student’s T); BJ hTRT+ exceeded maximal BJ lifespan (85–90 PD) by average 36 PD (P<10^-6); normal karyotype (46 chromosomes, no G-banding abnormalities in 2 RPE + 2 BJ clones); no loss of contact inhibition or growth in low serum; nude-mouse tumor assay not performed · archive: local PDF available ↩
doi:10.1002/emmm.201200245 · Bernardes de Jesus B, Vera E, Schneeberger K, Tejera AM, Ayuso E, Bosch F, Blasco MA · in-vivo · EMBO Mol Med 2012 · 4:691–704 · model: >95% C57BL/6 background mice; AAV9-mTert IV (2×10^12 vg/mouse) at 1 yr (eGFP n=12, mTERT n=21, control n=43) or 2 yr (eGFP n=14, mTERT n=23, control n=29) · +24% median lifespan extension (1-yr cohort, p=0.02 eGFP vs mTERT Log Rank); +13% (2-yr cohort, p=0.05 Log Rank); improved femur BMD, insulin sensitivity, neuromuscular coordination (Rota-Rod, Tightrope); cancer incidence not increased (p=0.87, Fisher’s exact); negative-control catalytically-inactive mTERT-DN showed no benefit · archive: local PDF available (gold OA) ↩

🧬 Aging Wiki

Explorer

telomerase-pathway