Humza M. Ashraf, Brianna Fernandez, Sabrina L. Spencer

Distinguishing quiescence from senescence is challenging due to overlapping biomarkers. Using single-cell time-lapse imaging, we revealed that staining intensity of senescence biomarkers reflects the duration of cell-cycle withdrawal rather than senescence itself. Our findings suggest that quiescence and senescence exist on a continuum of cell-cycle withdrawal, where biomarker intensities indicate the likelihood of cell-cycle re-entry.

Mario Leutert, Joe Armstrong, Anja R. Ollodart, Kyle Hess, Michael Muir, Ricard A. Rodriguez-Mias, Matt Kaeberlein, Maitreya Dunham, Judit Villén

A comprehensive study examined proteomic changes in aging Saccharomyces cerevisiae. Proteome dimensions related to function, including abundance, turnover, thermal stability, and phosphorylation, were analyzed. Findings revealed cumulative dysregulation of complex assemblies, mitochondrial remodeling, energy-metabolic shifts, and activation of signaling pathways. Caloric restriction mitigated age-dependent proteome changes, improving mitochondrial maintenance and protein biogenesis. The study offers valuable insights into aging mechanisms through thousands of age-dependent molecular events.

Isabel M. Serrano, Misa Hirose, Clint Valentine, Sharie Austin, Elizabeth Schmidt, Gabriel Pratt, Lindsey Williams, Jesse Salk, Saleh Ibrahim, Peter H. Sudmant

This study used ultra-sensitive Duplex Sequencing to profile ~2.5 million mt-genomes in young and aged mice to investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mt-genome in different tissues throughout aging. Distinct mutational patterns, hotspots, and positive selection were observed, along with somatic reversion mutations realigning mito-nuclear ancestry. Findings highlight the dynamic and selection-driven nature of mitochondrial genomes throughout an organism's lifespan.

Michael Ben Ezra, Jonas Bach Garbrecht, Nasya Rasmussen, Indra Heckenbach, Michael A. Petr, Daniela Bakula, Laust Mortensen, Morten Scheibye-Knudsen

Using 33 million histological samples, age- and mortality-associated features were extracted from text narratives (The Human Pathome). Sexual dimorphism in aging was observed. Machine learning was used to identify predictive terms and themes that predict aging and mortality. Nintedanib emerged as a potential aging intervention, reducing senescence markers, pro-fibrotic genes, and extending fruit fly lifespan. Expanding population datasets holds promise for discovering novel aging interventions.

Taruna Pandey, Bingying Wang, Jenny Zu, Huichao Deng, Kang Shen, Goncalo Dias do Vale, Jeffrey G. McDonald, Dengke K. Ma

This study demonstrates that an agonist insulin INS-7 is drastically over-produced and causes shortened lifespan in lpd-3 mutants, a C. elegans model of human Alkuraya-Kučinskas syndrome.