bims-ovagas Biomed News
on Ovarian aging and cGAS
Issue of 2026–03–15
eight papers selected by
Haiyuan Mu, Univeristy of California Berkeley
  1. Multicellular origins of murine ovarian inflammaging.
  2. The inflammatory clock: how cGAS-STING ticks in the aging ovary.
  3. Reproductive Challenges of the Ageing Female: A Comprehensive Narrative Review.
  4. Quality aging as an integrative concept in gerontology.
  5. Preventing ovarian aging: from redox-targeted strategies to extracellular vesicle-based therapies.
  6. Millions of sperm versus a few oocytes: would this evolutionary battle improve or impair spermatogenesis? A personal opinion.
  7. Single-Cell Spatial Proteomics Uncovers Molecular Interconnectivity among Hallmarks of Aging.
  8. Coordinating meiotic prophase i progression and early oocyte differentiation.
  1. Commun Biol. 2026 Mar 13.
    Multicellular origins of murine ovarian inflammaging.
    Anna Galligos, Joseph M Varberg, Wei-Ting Yueh, Aubrey Converse, Seth Malloy, Fatimah Aljubran, Francesca E Duncan, Jennifer L Gerton.
      Age-dependent reproductive decline has become a significant global health concern as the average maternal age at first birth increases. Fertility loss associated with reproductive aging is driven in part by alterations to ovarian composition and function, dysregulation of folliculogenesis, and increased inflammatory signaling. Our understanding of the molecular changes underlying ovarian aging has been expanded by single-cell and spatial transcriptomic studies, which identified infiltration of immune cells as a feature of ovarian aging. However, the function of these age-associated immune cells and their potential contributions to the inflammaging phenotype remain unclear. In this study, we integrate single-cell and spatial transcriptomics to define changes in the composition and intercellular signaling in the aging mouse ovary. We identify specific macrophage and T cell subpopulations that increase with age and are key sources of pro-inflammatory signaling in old ovaries. Further, we predict bidirectional signaling between these pro-inflammatory cells and granulosa cell populations that may impair follicular growth and development while promoting immune cell recruitment. These findings provide insights into the mechanisms that drive ovarian inflammaging.
    DOI:  https://doi.org/10.1038/s42003-026-09826-1
  2. Front Cell Dev Biol. 2026 ;14 1771546
    The inflammatory clock: how cGAS-STING ticks in the aging ovary.
    Yanjing Ma, Yu Chen, Xiong Yuan, Tingyu Li, Hao Luo, Yanfang Gu.
      Premature ovarian insufficiency (POI) is more than a fertility issue; it's a silent epidemic of accelerated systemic aging in young women, with current treatments failing to address its root cause. For too long, the relentless decline of ovarian function has been viewed as an inevitable mystery. But what if the ovary holds an internal "inflammatory clock," ticking away with each cellular insult and dictating the pace of its own decline? Here, we spotlight a surprising culprit: the cGAS-STING signaling pathway. Far beyond its day job in antiviral defense, this pathway emerges as a master integrator of ovarian aging. We reveal how stresses like DNA damage and mitochondrial dysfunction leak genetic material into the cell's interior, where cGAS-STING sounds a relentless alarm. This alarm does not just trigger inflammation; it initiates a vicious, self-amplifying cycle of cellular senescence, tissue fibrosis, and follicle destruction-a cycle that may explain why ovarian aging often feels like a one-way street. Therapeutically, we move beyond mere symptom management to explore strategies for resetting this inflammatory clock. We dissect both direct "brakes"-novel small molecules that silence cGAS or STING-and upstream "shields" that protect cellular powerplants and genome integrity. Most provocatively, we introduce the concept of "signal reprogramming": not just shutting down the pathway, but cleverly rewiring its output to favor repair over destruction. By repositioning cGAS-STING from a simple sensor to the central processor of ovarian aging, this review charts a course for a new class of therapeutics aimed at preserving ovarian function, not just managing its loss. The goal is no less than transforming our approach to women's reproductive longevity.
    Keywords:  cGAS-STING; inflammation; ovarian aging; premature ovarian insufficiency; therapeutic targets
    DOI:  https://doi.org/10.3389/fcell.2026.1771546
  3. BJOG. 2026 Mar 09.
    Reproductive Challenges of the Ageing Female: A Comprehensive Narrative Review.
    Sofia Bitzika, Meletios P Nigdelis, Angelos Daniilidis, Erich-Franz Solomayer, Irene Lambrinoudaki, Efstratios M Kolibianakis, Dimitrios G Goulis.
      Changes in societal norms over the last few decades have resulted in novel family planning trends, notably delayed childbearing and increased maternal age at the birth of the first child. Despite advances in reproductive medicine, ageing poses significant challenges. Natural conception in women ≥ 45 years of age is rare, with high rates of pregnancy loss, and assisted reproduction using autologous oocytes yields limited success. Oocyte donation offers higher live birth rates, exceeding 50%. Elective oocyte cryopreservation could aid in family planning; nevertheless, its success depends on the age at which cryopreservation is performed. These facts highlight the correlation between advancing age and a decline in oocyte quality and quantity. An age-related decline in endometrial receptivity could pose an additional barrier, although the evidence remains controversial. Furthermore, pregnancies in older women carry high risks for both the mother and child, which should be considered before assisted conception attempts. This comprehensive narrative review examines the advancements in assisted reproductive technology that have expanded the possibilities for delayed childbearing, while underlining at the same time the major challenges in the field. Innovations such as ovarian tissue cryopreservation and stem cell-based therapies have the potential to reshape reproductive options for these women. However, thorough counselling and tailored management remain of paramount importance.
    Keywords:  infertility: assisted conception; reproductive science: endometrial function; reproductive science: fertilisation; reproductive science: implantation; reproductive science: ovarian function
    DOI:  https://doi.org/10.1111/1471-0528.70197
  4. J Aging Stud. 2026 Mar;pii: S0890-4065(26)00011-3. [Epub ahead of print]76 101410
    Quality aging as an integrative concept in gerontology.
    Javier López, Gema Perez-Rojo, Cristina Noriega, Karl Pillemer.
      Our proposal of quality aging seeks to expand both successful aging and positive aging. Our aims include: to propose a construct that is not categorical but continuous or dynamic; to create an objective and measurable concept that avoids inducing feelings of guilt or inadequacy in those who may not appear to age positively or successfully; and to ensure a multidimensional construct. Our proposal of quality aging aims to highlight, from a psychosocial perspective, both the role of the environment and personal psychological resources. The intention of this model is to counteract the tendency in gerontology to emphasize the false dichotomy between positive and negative aging. We hope that the FRAG (Family functioning, Resilience, Acceptance and Gratitude) model could help correct some dualisms (positive vs. negative aging, healthy vs. unhealthy, environment vs. psychological emphasis), encourage investigation into the determinants of quality aging, and identify goals for older adults' interventions. Family functioning, resilience, acceptance, and gratitude are essential strengths to promote quality aging, which moves away from the idea that aging necessarily means loss, illness, or vulnerability. Physical health is important among older adults, but environmental and psychological aspects promote quality aging even in adverse health conditions. It is possible that facing adversities throughout the aging process may make older adults stronger.
    Keywords:  Aging model; Experiential acceptance; Family function; Gratitude; Resilience
    DOI:  https://doi.org/10.1016/j.jaging.2026.101410
  5. Front Aging. 2026 ;7 1707614
    Preventing ovarian aging: from redox-targeted strategies to extracellular vesicle-based therapies.
    Chiara Camerano Spelta Rapini, Camila Cecilia Rojo-Fleming, Chiara Di Berardino, Alessia Peserico, Giulia Capacchietti, Umberto Tosi, Nicola Bernabò, Mauro Mattioli, Barbara Barboni.
      Ovarian aging is increasingly recognized as a dynamic and modifiable process influenced by oxidative stress, mitochondrial dysfunction, and chronic inflammation. This review outlines the mechanisms by which environmental and lifestyle factors, such as smoking, high-fat diets, endocrine-disrupting chemicals, and micro- and nanoplastics (MNPs), contribute to accelerated ovarian decline and premature reproductive senescence. The distinction between physiological aging and pathological processes such as "inflamm-aging" is discussed, with particular attention to redox imbalance and mitochondrial impairment as key drivers of follicular depletion and endocrine dysfunction. Insights from experimental models of premature ovarian insufficiency and polycystic ovary syndrome are summarized to illustrate the role of reactive oxygen species and oxidative damage. Current antioxidant-based strategies aimed at delaying ovarian aging are reviewed, including melatonin, N-acetylcysteine, coenzyme Q10, polyphenols, and vitamins C and E. Particular emphasis is placed on the emerging potential of stem cell-derived extracellular vesicles (EVs) as a novel, cell-free therapeutic approach. Preclinical evidence suggests that EVs can reduce oxidative stress, support mitochondrial function, and restore ovarian physiology. Overall, the review highlights how redox-targeted and EV-based interventions may offer promising avenues to preserve ovarian function and extend reproductive healthspan.
    Keywords:  extracellular vesicles (EVs); mitochondrial dysfunction; ovarian aging; ovarian dysfunction; oxidative stress
    DOI:  https://doi.org/10.3389/fragi.2026.1707614
  6. Reproduction. 2026 Mar 13. pii: xaag033. [Epub ahead of print]
    Millions of sperm versus a few oocytes: would this evolutionary battle improve or impair spermatogenesis? A personal opinion.
    Vikas Kumar Roy.
      From fish to mammals, oogenesis has evolved to produce fewer oocytes of the best quality, from approximately millions to a few or one in humans. However, vertebrates from fish to mammals produce an enormous number of sperm. This point of view proposes that because evolution is a continuous process, someday in the future, spermatogenesis will evolve similarly to oogenesis: fewer sperm of the best quality will be produced.
    Keywords:  Ovum; Quality; Sperm; Sperm maturation; Spermatogenesis
    DOI:  https://doi.org/10.1093/reprod/xaag033
  7. bioRxiv. 2026 Feb 28. pii: 2026.02.26.708335. [Epub ahead of print]
    Single-Cell Spatial Proteomics Uncovers Molecular Interconnectivity among Hallmarks of Aging.
    Seungmin Yoo, Christopher Young, Liying Li, Lingraj Vannur, Junming Zhuang, Fan Zheng, Meiying Wu, Julie K Andersen, Chuankai Zhou.
      Aging is accompanied by conserved hallmarks including genomic instability, epigenetic alterations, loss of proteostasis, and mitochondrial dysfunction, but how these processes emerge and become mechanistically linked remains unclear. Here we leverage a proteome-wide, single-cell, subcellular atlas of protein expression, localization, and aggregation across yeast replicative aging to map hallmark-linked remodeling in its spatial context. We identify hundreds of previously unappreciated molecular changes that underlie major hallmarks of aging and show that hallmark phenotypes frequently manifest as compartment-specific erosion of spatial confinement, relocalization, and aggregation. 91.6% human orthologs of these hallmark-linked yeast proteins also change during human aging. Integrating these spatial phenotypes reveals many molecular connections linking different hallmarks. Temporal analysis suggests that disorganization of nucleolar ribosome biogenesis, proteostasis decline, and mitochondrial dysfunction precede other hallmarks. Together, our findings substantially deepen the molecular underpinnings of aging hallmarks and provide a framework for linking them into a hierarchical sequence of cellular failures.
    DOI:  https://doi.org/10.64898/2026.02.26.708335
  8. Development. 2026 Mar 12. pii: dev.205203. [Epub ahead of print]
    Coordinating meiotic prophase i progression and early oocyte differentiation.
    Kimberly M Abt, Myles A Bartholomew, Anna E K Nixon, Hanna E Richman, Megan A Gura, Kimberly A Seymour, Richard N Freiman.
      Female reproductive senescence results from the regulated depletion of a finite pool of oocytes called the ovarian reserve. This pool of oocytes is initially established during fetal development, but the oocytes that comprise it must remain quiescent for decades until they are activated during maturation in adulthood. In order for developmentally competent oocytes to populate the ovarian reserve they must successfully initiate both meiosis and oogenesis. As the factors that regulate the timing and fidelity of these early events remain elusive, we assessed the precise function and timing of the transcriptional regulator TAF4b during meiotic prophase I progression in mouse fetal oocytes. Compared to matched controls, E14.5 Taf4b-deficient oocytes enter meiosis I in a timely manner; however, their subsequent progression through the pachytene-to-diplotene transition of meiotic prophase I is compromised. Moreover, this disruption of meiotic progression is associated with the reduced ability of Taf4b-deficient oocytes to repair double-strand DNA breaks. Transcriptional profiling of Taf4b-deficient oocytes reveals that between E16.5 and E18.5 these oocytes fail to properly coordinate the reduction of meiotic gene expression and the activation of oocyte differentiation genes.
    Keywords:  Female infertility; Fetal oocyte attrition; Meiosis; Oogenesis; Ovarian reserve; Transcription
    DOI:  https://doi.org/10.1242/dev.205203
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