Julia Majewska, Amit Agrawal, Avi Mayo, Lior Roitman, Rishita Chatterjee, Jarmila Kralova, Tomer Landsberger, Yonatan Katzenelenbogen, Tomer Meir-Salame, Efrat Hagai, Nemanja Stanojevic, Ido Amit, Uri Alon, Valery Krizhanovsky

Senescent cells evade immune clearance and accumulate in aging and chronic inflammation by upregulating programmed death-ligand 1 (PD-L1) via p16-mediated inhibition of CDK4/6. Macrophages expressing p16 create an immunosuppressive environment. Targeting PD-L1 with anti-PD-L1 antibody enhances cytotoxic T cell activity and eliminates p16, PD-L1-positive cells, providing a potential treatment for age-related diseases.

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.

Carolina Cano Macip, Rokib Hasan, Victoria Hoznek, Jihyun Kim, Louis E. Metzger IV, Saumil Sethna, Noah Davidsohn

Lifespan of aged mice was extended through systemic delivery of AAVs encoding an OSK system. The mice, at 124 weeks old, experienced a remarkable 109% increase in median remaining lifespan compared to wild-type controls. This intervention also improved various health parameters and frailty scores, suggesting the potential to enhance both lifespan and healthspan in aging individuals. Furthermore, significant epigenetic markers of age-reversal were observed in human keratinocytes expressing exogenous OSK, indicating the possibility of reversing age-related changes. These findings have significant implications for developing interventions to combat age-associated diseases in the elderly.

Peter Lenart, Sacha Psalmon, Benjamin D. Towbin

A mathematical model proposes that mortality results from two opposing processes: physiological decline with age and survival benefits from growth and learning. Simulations show learning accelerates slower aging but limits negligible senescence. These findings shed light on the complex relationship between learning, mortality, and aging evolution.

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.