Selected publication milestones through 9 October 2026. These dates identify source publication years, not priority claims or a comprehensive history.
1999 — Telomerase-null mouse stress and lifespan phenotypes; restricted genetic model. PMID 10089885.
2007 — Checkpoint p21 manipulation dissociates persistent telomere dysfunction from some tissue and survival effects. PMID 17143283.
2011 — Endogenous reactivation rescues a telomerase-deficiency model. PMID 21113150.
2012 — AAV-TERT tests intervention in adult and old mice. PMID 22585399.
2019 — Human genetic contrasts expose cardiovascular/cancer trade-offs. PMID 31444995.
2024 — Pharmacological TERT activation improves selected aged-mouse functions; mechanism separation remains open. PMID 38908367.
Mean LTL does not measure the critical shortest telomeres in every aging tissue.
Human telomerase-activator biomarker effects lack demonstrated ordinary-aging functional benefit.
Canonical telomere maintenance versus noncanonical TERT effects require selective separation.
Cancer initiation, genomic instability and regenerative failure create endpoint-specific trade-offs.
Independent ordinary-aging replication and longer functional/cancer follow-up are needed.
A randomized prospectively registered trial in older adults without telomere disorders, with tissue-specific critical-short-telomere engagement, a selective maintenance intervention and orthogonal mechanism controls, prespecified functional healthspan endpoints and sufficiently long cancer surveillance. Preclinical epistasis should first separate canonical telomere effects from noncanonical TERT actions.