Sanjay Kureel, Rosario Maroto, Simon Powell, Felix Margadant, Brandon Blair, Blake B. Rasmussen, Michael Sheetz

Senescent cells treated with low frequency ultrasound (LFU) resume growth and increased motility. LFU induces Ca2+ entry, enhances autophagy, and inhibits mTORC1, reversing several senescence markers. Repeated LFU treatments extend cell replicative limits without altering phenotype. Rejuvenation is enhanced by rapamycin and Rho kinase inhibition but blocked by Sirtuin 1, Piezo1, or TRPV1 inhibition.

Bonnie L. Walton, Rebecca Shattuck-Brandt, Catherine A. Hamann, Victoria W. Tung, Juan M. Colazo, David D. Brand, Karen A. Hasty, Craig L. Duvall, Jonathan M. Brunger

A synthetic receptor platform was developed to target cell therapies for osteoarthritis (OA) to damaged cartilage. Type II collagen-specific synNotch receptors enabled engineered mesenchymal stromal cells (MSCs) to activate only in response to cartilage degeneration, expressing therapeutic genes, reducing inflammation, and promoting cartilage repair, demonstrating targeted OA treatment potential.

Roy Maimon, Carlos Chillon-Marinas, Sonia Vazquez-Sanchez, Colin Kern, Kresna Jenie, Kseniya Malukhina, Stephen Moore, Jess Cui, Alexander Goginashvili, Siavash Moghadami, Alexander Monell, Melissa McAlonis-Downes, Christine Hong, Paymaan Jafar-Nejad, C. Frank Bennett, Quan Zhu, John Ravits, Don W. Cleveland, Bogdan Bintu

Researchers used single-cell spatial transcriptomics (MERFISH) to map neurogenic niches in young and aged murine brains, finding high PTBP1 levels in glia. Suppressing PTBP1 in quiescent glia reactivated them, converting them into neurons that migrated and became GABAergic neurons. This suggests PTBP1 reduction could induce neuron generation in aged brains, offering therapeutic potential.

Domenico Di Fraia, Antonio Marino, Jae Ho Lee, Erika Kelmer Sacramento, Mario Baumgart, Sara Bagnoli, Pedro Tomaz da Silva, Amit Kumar Sahu, Giacomo Siano, Max Tiessen, Eva Terzibasi-Tozzini, Julien Gagneur, Judith Frydman, Alessandro Cellerino, Alessandro Ori

In the aging brain of a short-lived killifish, researchers studied the transcriptome, translatome, and proteome. Aging causes a reduction in proteins rich in basic amino acids, independent of mRNA regulation and proteasome activity. Aberrant translation pausing reduces ribosome availability, leading to proteome remodeling. This highlights a vulnerability in the biogenesis of basic DNA/RNA binding proteins, potentially connecting various aging hallmarks.

Wan Jin, Jing Zheng, Yu Xiao, Lingao Ju, Fangjin Chen, Jie Fu, Hui Jiang, Yi Zhang

Accumulation of DNA G-quadruplexes (G4s) during cell replication drives aging mechanisms by delaying genome replication and impairing DNA re-methylation and histone modification recovery. This leads to loss of heterochromatin and progressive G4 accumulation on promoters. Mutations in G4-resolving enzymes accelerate aging, revealing a universal molecular mechanism conserved across various species.