Gene Therapy Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice

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.

Björn Schumacher, David Meyer

Aging clocks, based on age-dependent DNA methylation changes, allow age determination and assess intervention efficacy in aging processes. Despite debates on programmed aging, this study supports an evolutionary aging theory where stochastic variation accumulates post-reproduction, predicting age accurately. It suggests any data with a ground state at age zero can build accurate aging clocks.

Jinmei Li, Sandeep Kumar, Kirill Miachin, Nicholas L. Bean, Ornella Halawi, Scott Lee, JiWoong Park, Tanya H. Pierre, Jin-Hui Hor, Shi-Yan Ng, Kelvin J. Wallace, Niklas Rindtorff, Timothy M. Miller, Michael L. Niehoff, Susan A. Farr, Rolf F. Kletzien, Jerry Colca, Steven P. Tanis, Yana Chen, Kristine Griffett, Kyle S. McCommis, Brian N. Finck, Tim R. Peterson

BIOIO-1001, identified in a CRISPRa screen, impacts lipid metabolism via SIRT3 which intersects two key aging pathways, the mTOR/insulin and NAD+ pathways. In vivo testing reduced metabolic issues, inflammation, and fibrosis in NASH and ALS models, making it a versatile therapy fitting the geroscience hypothesis.

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.