bims-caglex 2026-06-21 papers

Trends Mol Med. 2026 Jun 17. pii: S1471-4914(26)00116-4. [Epub ahead of print]

Stacia P A Everts, Michael Florea, João Pedro de Magalhães.

Aging affects virtually all organs and biological processes, and age-related diseases remain the leading causes of death worldwide. Genetic factors play a central role in modulating lifespan, and discoveries in the genetic manipulation of the aging process in animal models have transformed our perception of aging. However, translating these findings into clinical therapies remains challenging. Recent breakthroughs demonstrate that gene therapies can directly target aging mechanisms. Single-gene therapies have ameliorated multiple age-related pathologies, such as pediatric Parkinson disease. In this review, we discuss recent advances and prospects for developing gene therapies for aging and age-related diseases, highlighting potential targets, delivery strategies, cellular rejuvenation, and lessons from long-lived species. Despite remaining challenges, longevity gene therapy offers a promising avenue to reprogram aging and delay age-related decline.

Keywords: AAV; geroscience; healthspan; lifespan; rejuvenation

DOI: https://doi.org/10.1016/j.molmed.2026.05.007

Cell Rep Med. 2026 Jun 15. pii: S2666-3791(26)00287-9. [Epub ahead of print] 102870

Intervening in aging and related diseases with gene therapy techniques.

Mengmeng Jiang, Jing Qu, Moshi Song, Guang-Hui Liu.

Aging is the primary risk factor for most chronic diseases, and the global rise in aging populations presents an escalating challenge due to functional decline and multimorbidity. Gene therapy provides a versatile framework for modulating aging-regulatory pathways, such as epigenetic regulation, telomere maintenance, and stress-response networks, with the potential to reshape aging trajectories. In this review, we provide an in-depth synthesis of the genetic and epigenetic determinants of aging and highlight advances in gene-based approaches, including genome editing, RNA modulation, and epigenetic reprogramming, all of which hold promise as geroprotective strategies. Furthermore, we discuss mechanistic insights, safety considerations, and translational frameworks, offering a broad, conceptually grounded overview to guide the development of aging gene interventions aimed at improving the healthspan and reducing age-associated dysfunction.

Keywords: age-associated diseases; aging; gene therapy; intervention

DOI: https://doi.org/10.1016/j.xcrm.2026.102870

Cell Chem Biol. 2026 Jun 18. pii: S2451-9456(26)00186-8. [Epub ahead of print]33(6): 748-766

Mechanisms and interventions of epigenetic aging.

Qingqing Chu, Yihang Li, Zeming Wu, Jing Qu, Guang-Hui Liu.

Increasing evidence suggests that epigenetic dysregulation is both a hallmark and a potential driving force of aging. As a multifactorial, non-linear, and systemic biological process, aging likely results from a progressive imbalance in a complex epigenetic network involving DNA, histones, RNA, and non-coding sequences. These interconnected alterations collectively lead to core aging features such as genomic instability, heightened inflammation, and loss of cellular identity. In this review, we highlight the central role of epigenetic mechanisms across different dimensions in cellular, tissue, and organismal aging. Furthermore, we discuss potential intervention strategies designed to counteract these epigenetic alterations, indicating both their promise and the associated challenges.

Keywords: age-related diseases; aging; epigenetic mechanisms; interventions; senescence

DOI: https://doi.org/10.1016/j.chembiol.2026.05.007

Front Genet. 2026 ;17 1836446

Turning back time: a comprehensive list of interventions that decrease next-generation epigenetic aging clocks in humans.

Adiv A Johnson, David A Sinclair.

Epigenetic aging clocks estimate age from DNA methylation patterns and have become central tools in longevity research. More recently, next-generation clocks have been developed to better compensate for the known divergence between chronological age and epigenetic age in ways that relate to lifestyle, health, and age-related disease. Although epigenetic clocks represent investigational biomarkers, these newer models are more strongly associated with all-cause mortality risk than first-generation clocks. As such, interventions that modify them are of interest. To test this, we performed a series of systematic searches and identified 41 human studies reporting the effects of interventions on at least one next-generation epigenetic clock. Our data suggest that a diverse range of pharmaceutical, lifestyle, supplementation, non-pharmaceutical clinical, and psychosocial interventions can decrease epigenetic age, including exercise, a plant-rich diet, the GLP-1 receptor agonist semaglutide, caloric restriction, ketamine, omega-3 fatty acids, a multivitamin-multimineral supplement, umbilical cord plasma, and the cholesterol-lowering drug pitavastatin. Nicotinamide riboside, rapamycin, senolytics, and several other interventions showed no detectable effect, whereas plasmapheresis and other therapeutics accelerated epigenetic aging. We also summarize reported effect sizes and compare next-generation clocks with respect to their frequency of use and responsiveness to intervention.

Keywords: aging biomarker; biohorology; clinical trials; epigenetic age reversal; epigenetic aging clock; next-generation clock

DOI: https://doi.org/10.3389/fgene.2026.1836446