bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2025–08–24
six papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. An energy metabolism-engaged nanomedicine maintains mitochondrial homeostasis to alleviate cellular ageing.
  2. Pathological aging is alleviated by neutralization of the autophagy-repressive tissue hormone DBI/ACBP.
  3. A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline.
  4. Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment.
  5. Advances in the application of multi-omics analysis in skin aging.
  6. Turning back time: Aging plasticity and its rejuvenation.
  1. Nat Nanotechnol. 2025 Aug 19.
    An energy metabolism-engaged nanomedicine maintains mitochondrial homeostasis to alleviate cellular ageing.
    Liyuan Chen, Yijie Fan, Nan Jiang, Xiaoshuai Huang, Min Yu, He Zhang, Zhengren Xu, Danqing He, Yu Wang, Chengye Ding, Xiaolan Wu, Chang Li, Shiying Zhang, Hangbo Liu, Xinmeng Shi, Fanghui Zhang, Ting Zhang, Dan Luo, Cunyu Wang, Yan Liu.
      Energy restriction is closely related to cellular senescence and species longevity. Here, based on the structure and function of ATP synthase, a key enzyme for energy generation, we develop energy metabolism-engaged nanomedicines (EM-eNMs) to rejuvenate aged stromal/stem cells, and help to prevent skeletal ageing. We show that EM-eNMs infiltrate the mitochondria of aged bone marrow mesenchymal stromal/stem cells (BMMSCs), driving mitochondrial fission, mitophagy, glycolysis and maintaining BMMSC stemness and multifunction. The EM-eNMs directly bind to the ATP synthase and promote mitophagy through induction of the dynamin-related protein 1 (DRP1) gene. Remarkably, EM-eNMs selectively target bone tissues through systemic delivery and significantly reverse osteoporotic bone loss in aged mice by enhancing mitochondrial fission and mitophagy, while simultaneously restoring the stemness and osteogenic potential of aged BMMSCs in situ. Taken together, our findings highlight the potential of the EM-eNMs as a targeted therapy to alleviate cellular senescence and age-related diseases.
    DOI:  https://doi.org/10.1038/s41565-025-01972-7
  2. Autophagy. 2025 Aug 19.
    Pathological aging is alleviated by neutralization of the autophagy-repressive tissue hormone DBI/ACBP.
    Léa Montégut, Flavia Lambertucci, Lucas Moledo-Nodar, Isabelle Martins, Alejandro Lucia, Clea Barcena, Guido Kroemer.
      DBI/ACBP (diazepam binding inhibitor, acyl CoA-binding protein) is a macroautophagy/autophagy-inhibitory tissue hormone produced by multiple cell types. The plasma levels of DBI/ACBP rise with age and disease. In centenarians living in nursing homes, DBI/ACBP concentrations are approximately threefold higher than in younger adults (30-48 years old), but these levels increase further in centenarians hospitalized due to disease exacerbation. Elevated DBI/ACBP correlates with unfavorable clinical parameters, including high Charlson Comorbidity Index, elevated neutrophil:lymphocyte ratio, and decreased renal function. In mouse models, neutralization of DBI/ACBP using monoclonal antibodies ameliorates several aging-related pathologies. In zmpste24-/- progeroid mice, anti-DBI/ACBP therapy improves posture, mobility, cutaneous and dental abnormalities, splenic atrophy, kidney function, and blood parameters. In models of renal aging induced by cisplatin or doxorubicin, DBI/ACBP neutralization suppresses renal fibrosis and cellular senescence. Similarly, in cardiac and hepatic aging models, anti-DBI/ACBP reduces expression of the senescence marker CDKN1A/p21 (cyclin dependent kinase inhibitor 1A) in cardiomyocytes and hepatocytes. Single-nucleus RNA sequencing of heart tissue revealed that anti-DBI/ACBP restores key metabolic and cardioprotective gene expression patterns suppressed by doxorubicin. Together, these findings establish DBI/ACBP as a marker and driver of pathological aging and demonstrate that its neutralization confers multi-organ anti-senescence effects. Thus, DBI/ACBP-targeting strategies hold therapeutic potential for improving healthspan.
    Keywords:  Chemotherapy; DNA damage; geroscience; heart failure senescence
    DOI:  https://doi.org/10.1080/15548627.2025.2549451
  3. Cell Discov. 2025 Aug 19. 11(1): 69
    A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline.
    Haozheng Li, Yuanming Zheng, Chunlei Yuan, Jiayi Wang, Xiaying Zhao, Ming Yang, Defei Xiong, Yenan Yang, Yunpeng Dai, Yiming Gao, Yuqi Wang, Lei Xue, Gang Wang.
      A hallmark of aging is chronic systemic inflammation, which is exacerbated by the hypersecretory aging phenotype known as the senescence-associated secretory phenotype (SASP). How the SASP is initiated to accelerate tissue inflammation and aging is an outstanding question in aging biology. Here, we showed that phosphorylation of the Mediator subunit MED15 at T603 is able to control the SASP and aging. Transforming growth factor-β selectively induces CDK1-mediated MED15 T603 phosphorylation to control SASP gene expression. The MED15 T603 dephosphorylated mutant (T603A) inhibits the SASP and cell senescence, whereas the T603 phosphorylation-mimicking mutant (T603D) has the opposite effect. Mechanistically, forkhead box protein A1 preferentially binds to unphosphorylated but not phosphorylated MED15 at T603 to suppress SASP gene expression. Notably, aging mice harboring dephosphorylated mutation in this phosphosite exhibit improved learning and memory through the attenuation of the SASP across tissues. Overall, our study indicates that MED15 T603 phosphorylation serves as a control switch for SASP production, which underlies tissue aging and cognitive decline and provides a novel target for age-related pathogenesis.
    DOI:  https://doi.org/10.1038/s41421-025-00820-1
  4. Nat Aging. 2025 Aug 19.
    Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment.
    Laura Remesal, Juliana Sucharov-Costa, Yuting Wu, Karishma J B Pratt, Gregor Bieri, Amber Philp, Mason Phan, Turan Aghayev, Charles W White, Elizabeth G Wheatley, Bende Zou, Brandon R Desousa, Julien Couthouis, Isha H Jian, Xinmin S Xie, Yi Lu, Jason C Maynard, Alma L Burlingame, Saul A Villeda.
      Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we identify ferritin light chain 1 (FTL1), an iron-associated protein, as a pro-aging neuronal factor that impairs cognition. Using transcriptomic and mass spectrometry approaches, we detect an increase in neuronal FTL1 in the hippocampus of aged mice, the levels of which correlate with cognitive decline. Mimicking an age-related increase in neuronal FTL1 in young mice alters labile iron oxidation states and promotes synaptic and cognitive features of hippocampal aging. Targeting neuronal FTL1 in the hippocampi of aged mice improves synaptic-related molecular changes and cognitive impairments. Using neuronal nuclei RNA sequencing, we detect changes in metabolic processes, such as ATP synthesis, and boosting these metabolic functions through NADH supplementation mitigated pro-aging effects of neuronal FTL1 on cognition. Our data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation.
    DOI:  https://doi.org/10.1038/s43587-025-00940-z
  5. Front Aging. 2025 ;6 1596050
    Advances in the application of multi-omics analysis in skin aging.
    Boquan Long, Weitian Pan, Shuozhong Wu, Qianye Nong, Wenhui Li, Siqi Chen, Hongwei Guo.
      Skin aging is a progressive decline in the structural integrity and physiological function of the skin, driven by a complex interplay of intrinsic and extrinsic factors. Consequently, skin aging is classified into intrinsic and extrinsic aging. Intrinsic aging is characterized by epidermal thinning, dryness, fine lines, and reduced elasticity over time, whereas extrinsic aging manifests as epidermal thickening, deep wrinkles, skin laxity, roughness, and pigmentation, particularly in sun-exposed areas, such as the face, neck, and hands. The underlying mechanisms of these two aging processes are intricate and distinct, encompassing various elements, including temporal aspects, genetic predisposition, immune responses, endocrine influences, and ultraviolet radiation. Multi-omics approaches-including macro-genomics, epigenetics, transcriptomics, proteomics, and metabolomics-offer valuable insights into the mechanisms and pathogenesis of skin aging while aiding in the identification of biomarkers and potential therapeutic targets. This review provides an overview of advancements in skin aging research using multi-omics technologies, aiming to foster innovation in research methodologies related to skin aging.
    Keywords:  anti-aging; biomarkers; multi-omics; pathogenesis; skin aging
    DOI:  https://doi.org/10.3389/fragi.2025.1596050
  6. Curr Opin Neurobiol. 2025 Aug 18. pii: S0959-4388(25)00128-X. [Epub ahead of print]94 103097
    Turning back time: Aging plasticity and its rejuvenation.
    Carola I Radulescu, Kjara S Pilch, Xingjian Wang, Fontaine Gibbs, Samuel J Barnes.
      As we age, our brain is influenced by experience and intrinsic biological changes. This combination of external and internal factors shapes the way in which our brain functions. Neuronal plasticity processes can store information about the sensory world and regulate neural-circuit activity levels to maintain stable neural-circuit function. These learning- and homeostasis-related plasticity processes exhibit age-related changes. Developing a better understanding of such age-related changes may open opportunities for rejuvenation strategies that promote plasticity and improve neurological health in later life. Here we review some of the latest work investigating age-related plasticity changes with a specific focus on sensory cortices. We propose that a better understanding of age-related tipping points in the context of plasticity could facilitate timed intervention strategies that may promote resilience during aging, by boosting the efficacy of endogenous plasticity mechanisms.
    DOI:  https://doi.org/10.1016/j.conb.2025.103097
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