bims-ovagas Biomed News
on Ovarian aging and cGAS
Issue of 2026–03–22
seven papers selected by
Haiyuan Mu, Univeristy of California Berkeley
  1. Mechanistic insights into aging and longevity: Implications for ovarian function and health.
  2. Femoral fracture leads to moderate pulmonary organ damage in aged mice and induces immune alterations.
  3. Metabolic, epigenetic, and immune crosstalk in ovarian aging.
  4. What we could not have known: ovarian cycles, follicle development, and the signature of life.
  5. Anti-Müllerian hormone (AMH): Decoding its role in fertility assessment, reproductive health and beyond.
  6. Smooth muscle cell estrogen receptor alpha promotes arterial stiffness in the absence of estradiol.
  7. Immune cytokines as a bridge linking the gut-liver-ovary axis in the pathogenesis of premature ovarian failure.
  1. Tissue Cell. 2026 Mar 13. pii: S0040-8166(26)00166-7. [Epub ahead of print]101 103473
    Mechanistic insights into aging and longevity: Implications for ovarian function and health.
    Abdel Halim Harrath.
      Ovarian aging is characterized by progressive follicular reserve depletion, mitochondrial dysfunction, oxidative stress, and endocrine decline. This review examines the molecular mechanisms driving ovarian aging and evaluates emerging therapeutic strategies to preserve reproductive longevity. Key mechanistic contributors include telomere attrition, accumulated DNA damage, impaired autophagy, chronic inflammation, and dysregulation of major longevity pathways such as PI3K/AKT/mTOR, AMPK, and sirtuins. Disruption of these interconnected signaling networks accelerates follicular activation, granulosa cell apoptosis, and oocyte quality decline. We further discuss targeted interventions aimed at modulating these pathways, including mTOR inhibitors, AMPK activators, antioxidants, mitochondrial protectants, autophagy regulators, and select nutraceuticals. Compounds such as rapamycin, metformin, resveratrol, and melatonin demonstrate mechanistic promise in preclinical and emerging clinical studies. Nutritional and lifestyle modifications may complement pharmacological approaches. Collectively, advancing mechanistic understanding of ovarian aging provides a foundation for developing precision strategies to delay menopause, preserve fertility, and improve women's healthspan.
    Keywords:  Autophagy; Longevity; Ovarian aging; Oxidative stress; PI3K/AKT/mTOR; Therapeutic interventions
    DOI:  https://doi.org/10.1016/j.tice.2026.103473
  2. Front Immunol. 2026 ;17 1763857
    Femoral fracture leads to moderate pulmonary organ damage in aged mice and induces immune alterations.
    Jasmin Maria Bülow, Helen Rinderknecht, Alessa Wagner, Melanie Haffner-Luntzer, Katrin Bundkirchen, Claudia Neunaber, Borna Relja, Nils Becker.
       Introduction: The relevance of age-related immunological alterations in patients experiencing fractures has drastically increased due to the global rise in life expectancy and the elevated risk of fractures among elderly individuals. The potential cross talk between long-bone fractures and the respiratory system is particularly crucial, given the high incidence of healthcare-associated pneumonia and its impact on mortality in aged patients with fractures.
    Method: Age-dependent differences in lung inflammation and regeneration following fracture were investigated using male C57BL/6J mice aged 17-26 weeks (young) and 64-72 weeks (aged), which underwent a unilateral femur osteotomy with external fixation (Fx) or sham surgery.
    Results: Fracture leads to an altered inflammatory response and expression of regeneration-associated pathways in the lung of both young and aged mice, as reflected by reduced levels of pro- and anti-inflammatory cytokines IL-6, MCP-1, and IL-10, along with increased gene expression of sclerostin, a regulator of Wnt signaling. In addition, aged mice showed increased CXCL1 levels, resulting in enhanced pulmonary neutrophil infiltration following fracture. This was associated with increased pulmonary damage, as evidenced by heightened RAGE and total protein BAL levels.
    Conclusion: Our data suggests that femoral fracture in the elderly impairs lung inflammatory regulation and early regeneration, which potentially increase the risk of pulmonary complications.
    Keywords:  Wnt; age; cytokines; fracture; inflammation; neutrophils
    DOI:  https://doi.org/10.3389/fimmu.2026.1763857
  3. iScience. 2026 Mar 20. 29(3): 114733
    Metabolic, epigenetic, and immune crosstalk in ovarian aging.
    Jing Li, Qianhui Liao, Yan Yang, Kang Wang, Weiai Liu, Fang Zhou, Huiping Liu, Ye Zhang.
      Ovarian aging, marked by follicle depletion and oocyte quality decline, involves complex metabolic alterations. This review synthesizes evidence that dysregulated metabolic reprogramming, encompassing energy, lipid, and nutrient metabolism, drives ovarian functional decline. Central to this process is a self-reinforcing "metabolism-epigenetics-immunity" triangular network, where mitochondrial dysfunction and NAD+ depletion disrupt epigenetic regulation and activate chronic inflammation, collectively accelerating follicular atresia and hormonal dysfunction. By integrating this mechanistic framework, we highlight emerging intervention strategies targeting metabolic hubs, such as mitochondrial rescue and senescent cell clearance, which offer new avenues for preserving ovarian function. This work provides a conceptual foundation for developing personalized strategies to mitigate reproductive aging and its systemic health impacts.
    Keywords:  epigenetics; human metabolism; immunity
    DOI:  https://doi.org/10.1016/j.isci.2026.114733
  4. Mol Hum Reprod. 2026 Jan 07. pii: gaag010. [Epub ahead of print]32(1):
    What we could not have known: ovarian cycles, follicle development, and the signature of life.
    Teresa K Woodruff.
      Reproductive science is a discipline of generation and for generations. Our work has focused on the signals that drive reproductive cycles at the organismal and the organ level. The principal endocrine signals of male and female reproductive cycles include inhibin and activin, traditional peptide hormones, and at the cellular level, zinc, a workhorse element now elevated to the role of a signal on par with phosphate and calcium. Our studies relied on and built technologies to make our discoveries, including enzymatic sequencing and PCR, alginate beads and microfluidics, and sophisticated elemental imaging and quantitation. Taken together, we described the molecular basis of negative feedback by inhibin in the ovary, engineered ex vivo environments for ovarian follicle development, and discovered the first external signal of a new organism, the zinc spark. Some of this work is being applied to patients who are in danger of losing their fertility in a variety of settings, including during cancer care, a medical field called oncofertility. Advances in reproductive science beckon us to see ourselves in the future, and with the discoveries described here, our view extends further.
    Keywords:   in vitro follicle growth; EVATAR; activin; follicle; inhibin; microfluidics; oncofertility; zinc spark
    DOI:  https://doi.org/10.1093/molehr/gaag010
  5. Int J Biol Macromol. 2026 Mar 12. pii: S0141-8130(26)01304-8. [Epub ahead of print] 151378
    Anti-Müllerian hormone (AMH): Decoding its role in fertility assessment, reproductive health and beyond.
    Prasanna Pal, Fanny Josan, Sonam Yadav, Syed Azmal Ali.
      Anti-Müllerian Hormone (AMH) is a critical regulator of reproductive processes and has emerged as a valuable tool in fertility assessment and reproductive health. This comprehensive review provides a detailed exploration of AMH, encompassing its discovery, structural characteristics, and diverse applications in reproductive medicine. The historical background of AMH, structural features including its dimeric glycoprotein composition and variations in amino acid sequences among different species, are highlighted. The role of AMH in fetal development, specifically in males, is examined. The review then delves into the expression patterns of AMH during follicular development. The review explores external factors influencing AMH secretion, including nutrition, hormonal regulation, and endocrine disruptors, along with its association with reproductive disorders. The diagnostic and prognostic utility of AMH is highlighted, emphasizing its superior specificity and sensitivity over other biomarkers. The heritability of AMH and its relevance for genetic selection in domestic animals are discussed, positioning it as a key marker for reproductive traits. Advances in AMH assays, particularly ELISA, are outlined with relevance to clinical and field applications. This comprehensive review underscores AMH's multifaceted role in fertility assessment and reproductive health, while also identifying future research prospects and its potential in personalized reproductive medicine.
    Keywords:  Anti-Müllerian hormone; Biomarker; Fertility; Livestock; Ovarian reserve; Reproductive disorders; Reproductive management
    DOI:  https://doi.org/10.1016/j.ijbiomac.2026.151378
  6. bioRxiv. 2026 Mar 05. pii: 2026.03.03.709417. [Epub ahead of print]
    Smooth muscle cell estrogen receptor alpha promotes arterial stiffness in the absence of estradiol.
    Casey G Turner, Jacqueline Matz, Jade Breton, Karla C de Oliveira, Rachel Kenney, Jennifer Vorn, Michelle Zhao, Jaime Ibarrola, Qing Lu, Gregory Martin, Zhe Sun, Iris Z Jaffe, Michael A Hill, Jennifer J DuPont.
       Background: Clinical evidence supports a greater impact of arterial stiffening in cardiovascular mortality in women versus men. Arterial stiffness increases across the menopausal transition, implicating a role of the loss of estrogens in arterial stiffening, but mediating mechanisms remain unclear.
    Methods: The role of estradiol and smooth muscle cell (SMC) estrogen receptor alpha (ERα) in arterial stiffening, by aortic pulse wave velocity (PWV), was assessed in 3 models: (1) the loss of estradiol in young, female mice comparing sham surgery or bilateral ovariectomy (OVEX) ± estradiol, (2) the impact of sham versus OVEX surgery in young, female SMC-ERα-intact and SMC-ERα-knockout (KO) littermates, and (3) arterial stiffening during natural aging by comparing young and aged, female and male SMC-ERα-intact and SMC-ERα-KO littermates. Mechanistic pathways were assessed using histological assessment of aortic fibrosis and elastin degradation, aortic MMP expression, and atomic force microscopy.
    Results: OVEX increased PWV and aortic medial fibrosis, with no impact on elastin integrity, in young female mice. Arterial stiffening and fibrosis were prevented in OVEX mice that were supplemented with estradiol. OVEX-induced arterial stiffening in SMC-ERα-intact female mice was prevented in SMC-ERα-KO littermates. In this model, OVEX was also associated with increased aortic medial fibrosis without changes in elastin integrity. Aging from 3 to 18 months significantly increased PWV in female and male SMC-ERα-intact mice. Aging-induced stiffening was fully prevented in female and partially prevented in male SMC-ERα-KO mice. SMC-ERα contributes to aging-associated arterial stiffening by sex-specific mechanisms, including elastin degradation in females and phenotypic changes in SMC stiffness and probability to form cellular adhesions in males. Circulating estradiol was significantly decreased in serum from aged compared with young female mice.
    Conclusions: These findings support that SMC-ERα contributes to arterial stiffening in female and male mice in situations where the vasculature is exposed to low levels of estradiol.
    DOI:  https://doi.org/10.64898/2026.03.03.709417
  7. Front Endocrinol (Lausanne). 2026 ;17 1758707
    Immune cytokines as a bridge linking the gut-liver-ovary axis in the pathogenesis of premature ovarian failure.
    Huimin Xu, Muxi Li, Shouyan Yang, Deyou Jiang.
      Premature ovarian failure (POF) is a multifactorial disorder characterized by the progressive decline of ovarian function, in which autoimmune factors account for approximately 10%-30% of cases. Accumulating evidence has demonstrated that immune-related mediators, including regulatory T cells (Tregs), interferon-γ (IFN-γ), and T helper 17 (Th17) cells, play pivotal regulatory roles in its initiation and progression. In recent years, the gut-liver axis and its potential mechanistic links with POF have emerged as a research hotspot in this field. Notably, these pathways are closely associated with the expression and functional balance of key immune mediators such as Tregs, IFN-γ, and Th17 cells. Based on the bridging role of immune cytokines between POF and the gut-liver axis, we propose a novel conceptual framework in which immune cytokines serve as a central hub to systematically elucidate the intrinsic connections among POF, gut microbiota dysbiosis, and bile acid metabolism. Furthermore, we highlight the current limitations of existing studies in this area. This perspective may provide a new theoretical framework for understanding the pathogenesis of POF and holds significant scientific value. Importantly, it may also offer novel insights and potential evidence for expanding clinical diagnostic and therapeutic strategies.
    Keywords:  POF; bile acid metabolism; gut microbiota; immunity; mechanistic insights
    DOI:  https://doi.org/10.3389/fendo.2026.1758707
This page is being maintained by Thomas Krichel. It was last updated on 2026‒03‒22 at 20:22.