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Open research questions in Telomeres, Telomerase, and Senescence

633 gap statements mined from Telomeres, Telomerase, and Senescence papers in our 7.9M-paper local library, which holds 2,124 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • As populations worldwide continue to age, the burden of chronic, age-related diseases has become an urgent global challenge. Cellular senescence and SASP have emerged as central players in the aging process, primarily by initiating pro-inflammatory states that compromise tissue function.

    The vicious cycle of SASP and inflammaging promotes aging and age-related diseases · 2026 · DOI

  • Cellular senescence and DNA damage are central drivers of aging; however, how epigenetic mechanisms intersect with these processes remains incompletely understood.

    LSD1-mediated demethylation of the DNA damage response factor ATM promotes senescence and organ aging · 2026 · DOI

  • Future studies should focus on elucidating the detailed mechanisms through which HPS modulates AMPK activity and its downstream effects on autophagy, metabolism, and regenerative processes, thereby paving the way for the development of HPS-based interventions against liver aging and related pathologies.

    Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK · 2026 · DOI

  • In interpreting apparently conflicting findings, consideration was given to differences in tumor type, treatment modality, experimental model, senescence definition and biomarkers, cellular compartment examined, timing of sample collection, and clinical endpoint.

    Therapy-Induced Senescence in Cancer Treatment Resistance: Mechanisms, Evidence, and Translational Opportunities · 2026 · DOI

  • Given the limited knowledge on the safety and efficacy of these therapies in the context of atherosclerosis, further research on senescence markers, intervention selectivity, and the impact of SASP and senescent cells on the vascular microenvironment is necessary to develop safe and personalized therapeutic strategies.

    The Role of Cellular Senescence and SASP in the Pathogenesis of Atherosclerosis and the Therapeutic Potential of Senolytic Strategies in Cardiovascular Diseases · 2026 · DOI

  • The convergence of association patterns, functional annotation, and biological context suggests that this locus warrants further investigation as a potential regulatory modifier in familial EOAD, possibly through mechanisms related to telomere maintenance and epigenomic organization.

    Regulatory Variation at TERT and TERC Shows Limited Association with Early-Onset Alzheimer’s Disease in Carriers of the Mexican Founder Mutation PSEN1 A431E · 2026 · DOI

  • Future studies should prioritize direct quantification of telomere length—such as by relative qPCR or Southern blot—to determine whether the genotype-level association observed for rs12696304 operates primarily through modulation of TERC expression, AC-TRT3, or both.

    Regulatory Variation at TERT and TERC Shows Limited Association with Early-Onset Alzheimer’s Disease in Carriers of the Mexican Founder Mutation PSEN1 A431E · 2026 · DOI

  • Because comparatively little is known about telomerase in the plant kingdom, we employed an unbiased qMS approach to investigate whether RNP assembly and regulatory mechanisms similar or divergent to other eukaryotic lineages exist for Arabidopsis telomerase.

    La1: an evolutionarily conserved player in the Arabidopsis telomerase complex · 2026 · DOI

  • Preclinical work in mouse models has demonstrated that sequential or simultaneous treatment with senolytic and senomorphic agents can produce than either greater approach alone, though the optimal sequencing, dosing intervals, and tissue contexts for such regimens are not yet established.

    Silencing without clearing: pharmacological modulation of the SASP in aging and disease · 2026 · DOI

  • Finally, it remains possible that severe fibrosis secondarily impairs RiBi, creating a feed-forward loop that amplifies fibrogenesis, and thus warrants further exploration.

    Defective Ribosome Biogenesis Drives Tubular Senescence and Renal Fibrosis via IRBC–p53 Activation · 2026 · DOI

  • Our findings highlight ectopic olfactory receptor signaling as an underexplored mechanism of tumor suppression and provide in vitro evidence for a sequential approach in CRC in which β-ionone-mediated OR51E2 activation induces a senescence-like state followed by senolytic treatment.

    Olfactory Receptor 51E2 Activation by β-Ionone Induces a Senescence-Like Phenotype and Increases Susceptibility to Senolytic Treatment in Colorectal Cancer · 2026 · DOI

  • Although its biological impact as a hallmark of cancer is becoming increasingly understood across various malignancies, the specific role of cellular senescence in driving the immunosuppressive landscape of triple‐negative breast cancer (TNBC) remains to be fully elucidated.

    SP1‐Driven SPP1 + Senescent Macrophages Orchestrate an Immunosuppressive Microenvironment in Triple‐Negative Breast Cancer · 2026 · DOI

  • In parallel, clinical trial design in geroscience must undergo innovation to accommodate the unique challenges of targeting aging biology. Traditional trial endpoints, such as disease incidence or short-term symptom resolution, may not fully capture the long-term benefits of senotherapeutics.

    Targeting Senescence: A Review of Senolytics and Senomorphics in Anti-Aging Interventions · 2025 · DOI

  • ECM deposits in the form of guttae are key clinical features of FECD, however, the mechanisms underlying their formation, progression, and contribution to disease pathophysiology remain poorly understood.

    Permanent Senescence Via p16 Leads to Guttae Formation in an In Vitro Human Corneal Endothelial Cell Model · 2025 · DOI

  • A promising avenue for future research is to determine whether shelterin-related complexes act as intermediaries or modulators of the effects of Astragalus membranaceus and its derivatives on telomerase function.

    Targeting Telomere Shortening in Vascular Aging and Atherosclerosis: Therapeutic Promise of Astragalus membranaceus · 2025 · DOI

  • To unravel the complexities of the involved molecular pathways and to explore potential therapeutic interventions targeting the Nrf2-ARE pathway for ameliorating the detrimental consequences of unhealthy aging, further in-depth investigations are warranted.

    Accelerated Aging Induced by an Unhealthy High-Fat Diet: Initial Evidence for the Role of Nrf2 Deficiency and Impaired Stress Resilience in Cellular Senescence · 2024 · DOI

  • Maternal age has always been a risk factor for adverse birth outcomes, all of which are associated with the shortening of telomere length, and whether it may interact with OCP exposure on adverse health effects remains to be clarified in future studies.

    Association Between Prenatal Exposure to Organochlorine Pesticides and Telomere Length in Neonatal Cord Blood · 2024 · DOI

  • Future research is needed to define an exact mechanism that explains the stronger correlation between Cd and TL. Evidence for Inverse Correlation Between Cadmium and Telomere Length There is very limited evidence on the toxic effects of metal exposures and TL alterations.

    Review of Correlations Between Telomere Length and Metal Exposure Across Distinct Populations · 2024 · DOI

  • However, current limitations, including cohort heterogeneity, variable biomarker platforms, limited longitudinal sampling, and lack of standardized thresholds, preclude immediate routine bedside implementation of some of the biomarkers presented in this review.

    Deep Biological Clocks in Critical Care Medicine: A Scoping Review Toward Translational Precision Care · 2026 · DOI

  • This real-world prescribing pattern limits the feasibility of assembling a sufficiently powered non-metformin diabetic comparator group, which is acknowledged as a practical limitation of the present study.

    Metformin exhibits gender specific impact on telomere dynamics by enhancing RAP1 expression in type-2 diabetes mellitus · 2026 · DOI

  • Whether the SA-b-Gal-associated survival differences observed here also occur in such settings remains to be established.

    SA-β-Gal stratification reveals senescence-associated heterogeneity and differential cell death susceptibility in human CD8 effector T cells · 2026 · DOI

  • Fourth, we lacked data on post-discharge parameters, including subclinical SARS-CoV-2 reinfections, rehabilitation status, vaccination, and concurrent long-term therapies, which could influence telomeric maintenance over time.

    Association of relative telomere length with glucocorticoid therapy in critically ill patients with severe COVID-19: a preliminary study · 2026 · DOI

  • It shows how these processes influence each other, contributing to cancer risk and chronic inflammation. The central role of telomerase and its relationship with telomeres is emphasized. In the present day, telomerase is recognized for its critical role in both cellular aging and cancer progression.

    Aging, Cancer, and Inflammation: The Telomerase Connection · 2024 · DOI

  • Accumulate in endothelium, smooth muscle cells, and macrophages; secrete pro-inflammatory SASP factors Amplifies inflammation, destabilises plaques; effects are context-dependent Reduce senescent cell burden, inflammation; potential to improve vascular/cardiac function Modulate SASP without cell removal; safer but do not eliminate source Lack of biomarkers, potential plaque destabilisation, limited clinical data…

    The Role of Cellular Senescence and SASP in the Pathogenesis of Atherosclerosis and the Therapeutic Potential of Senolytic Strategies in Cardiovascular Diseases · 2026 · DOI

  • Future research directions to enhance biomarker-based diagnostic technologies, - Research and clinical trials are underway for anti-miR-21 oligonucleotides and a chemically modified miR-21 inhibitor (ADM-21)-based inhibition…

    Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends · 2025 · DOI

Most-cited papers in Telomeres, Telomerase, and Senescence

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Open questions raised by papers listed on this page include: (1) Cellular senescence and DNA damage are central drivers of aging; however, how epigenetic mechanisms intersect with these processes remains incompletely understood (“LSD1-mediated demethylation of the DNA damage response factor ATM promotes…”, 2026); (2) Whether the SA-b-Gal-associated survival differences observed here also occur in such settings remains to be established (“SA-β-Gal stratification reveals senescence-associated heterogeneity and…”, 2026); (3) ECM deposits in the form of guttae are key clinical features of FECD, however, the mechanisms underlying their formation, progression, and contribution to disease pathophysiology remain poorly understood (“Permanent Senescence Via p16 Leads to Guttae Formation in an In Vitro Human…”, 2025); (4) Future research is needed to define an exact mechanism that explains the stronger correlation between Cd and TL (“Review of Correlations Between Telomere Length and Metal Exposure Across…”, 2024). 633 gap statements have been mined from Telomeres, Telomerase, and Senescence papers in our 7.9M-paper local library, which holds 2,124 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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