bims-caglex 2026-07-26 papers

Front Cell Dev Biol. 2026 ;14 1824533

Young cardiac telocyte-derived exosomes rejuvenate aging hearts in rats.

Luocheng Lv, Yu Zhu, Yanjun Chen, Xin Zheng, Ruijin Huang, Hui Zhao, Ziqiang Yuan, Shanshan Feng, Xufeng Qi, Yilin Chen, Zhaofu Liao, Dongqing Cai.

Background and objective: Effective clinical strategies for rejuvenating aging hearts are needed to reverse and cure aging-related pathological cardiac degeneration. The present study was designed to investigate the potential rejuvenating effects of young cardiac telocyte (CT)-derived exosomes (Y-CT-exos) on cardiac aging and aging-related pathological cardiac degeneration.
Methods: Y-CT-exos were prepared from young CTs. Twenty-four-month-old female Sprague‒Dawley rats were used as an aged model to evaluate the benefits of Y-CT-exos on cardiac aging and aging-related pathological cardiac degeneration. Nanoparticle tracking analysis, zeta potential measurements, Western blotting, qPCR, β-gal, ROS and PKH26 staining, multiplex immunoassays, Masson's trichrome and immunohistochemical staining, motor function tests, wheat germ agglutinin staining and echocardiography, etc., were performed to evaluate the quality and distribution of the Y-CT-exos and their effects against cardiac aging. RNA sequencing was performed to compare the changes in the transcriptomes between aged hearts and Y-CT-exos-treated aged hearts, and differentially expressed genes (DEGs) were identified. Ingenuity pathway analysis (IPA) was used to identify related genes, their associated pathways, and the up- and downstream interaction networks underlying the rejuvenating effects of Y-CT-exos on cardiac aging and cardiac pathological improvement.
Results: Y-CT-exos rejuvenated cardiac aging by ameliorating the senescence of cardiomyocytes and cardiac fibroblasts, the accumulation of DNA and ROS damage in cardiomyocytes, inflammation in the hearts and body of aged rats, promoting the proliferation of cardiomyocytes, improving aging-related decreases in cardiac function, and alleviating cardiomyocyte hypertrophy and cardiac fibrosis. In addition, the related genes, their associated pathways and the up- and downstream interaction networks underlying the therapeutic effects of reversed cellular senescence (inhibition of the p38 MAPK signaling pathway and activation of the antioxidant function of vitamin C), inflammatory aging (inhibition of the inflammasome pathway), and cardiomyocyte hypertrophy, were revealed.
Conclusion: Y-CT-exos, the identified genes and their up- and downstream interaction networks, which are involved in the alleviation of cellular senescence, inflammatory aging and cardiomyocyte hypertrophy, have great potential for the development of novel cell-free therapies to rejuvenate aging hearts and ameliorate the aging-related decrease in cardiac function, cardiac hypertrophy and cardiac fibrosis.

Keywords: cardiac aging; cardiac telocytes; degenerative myocardiopathy; rejuvenation; young cardiac telocyte-derived exosomes

DOI: https://doi.org/10.3389/fcell.2026.1824533

Aging (Albany NY). 2026 Jul 17. 18(1): 868-892

Selective targeting of cancer and senescence via shared metabolic shifts extends lifespan of old mice.

Zachery R Robinson, Sabrina C Fong, Daniella Y Choi, Sophia Siopack, Alexander Bolanos-Campos, Negar Morshedian, Eva Utke, Mayuka Ninomiya Kanda, Cameron Kato, Michael J Conboy, Irina M Conboy.

Eliminating both senescent and cancer cells through pharmacological intervention presents a powerful therapeutic strategy against aging and tumor progression. Navitoclax has emerged as a promising candidate with both senolytic and antitumor activity, but its clinical application remains limited due to dose-dependent thrombocytopenia and tumor-specific resistance. To overcome these limitations, we combined dichloroacetate and metformin with a 10-fold reduced dose of Navitoclax (ABT-263) and show that this pharmacology, termed, DMA, selectively targets the metabolic vulnerabilities underlying senescent and malignant cells. We demonstrate that DMA effectively ablates different types of senescent and cancer cells in vitro by exacerbating their defects in ATP production. Notably, the treatment is well tolerated by healthy human cells and in mice in vivo, and in fact improves the functional performance of aged mice after acute administration and extends lifespan after prolonged dosing. While the in vivo effects of DMA are yet to be fully explored, our findings suggest that it might represent a new, clinically viable way to combat cancer and senescence without toxicity to healthy cells and tissues.

Keywords: ATP; aging; cancer; metabolic shift; senescence

DOI: https://doi.org/10.18632/aging.206399

Nat Aging. 2026 Jul 20.

Positioning TERT at the apex of aging.

Ronald A DePinho.

Aging is a biologically tractable process. Telomerase reverse transcriptase (TERT) has emerged as an upstream regulator coordinating several hallmarks of aging across preclinical models. Beyond maintaining telomeres, TERT influences mitochondrial health, epigenetic regulation, inflammation and stem cell function. Multiple translational strategies are being explored to modulate TERT. In mice and human cell models, restoration of physiological-range TERT expression characteristic of younger cells, or related telomere-focused interventions, has been associated with improvements in selected age-related phenotypes without a detectable increase in cancer. Simultaneously, human genetics links common variation in the TERT locus to increased risk of several cancers, underscoring the need for careful mechanistic and long-term safety evaluations. Together, mounting evidence indicates that TERT occupies an important position in aging biology with the potential to affect healthspan. This Perspective reviews current evidence for TERT's canonical and noncanonical roles and outlines a cautious therapeutic framework for evaluating TERT-directed geroprotective strategies.

DOI: https://doi.org/10.1038/s43587-026-01179-y