DNA repair and anti-cancer mechanisms in the longest-living mammal: the bowhead whale

Steve Horvath, Ezequiel Lacunza, Martina Canatelli Mallat, Enrique L. Portiansky, Maria D. Gallardo, Robert T. Brooke, Priscila Chiavellini, Diana C. Pasquini, Mauricio Girard, Marianne Lehmann, Qi Yan, Ake T. Lu, Amin Haghani, Juozas Gordevicius, Martin Abba, Rodolfo G. Goya

The injection of Yamanaka genes (OSKM) into the hippocampus of old rats significantly improved their spatial learning performance and potentially their spatial memory. Morphological changes were not observed in astrocytes or mature neurons, indicating the treatment caused no harmful brain changes. The analysis of differential methylation suggested a possible rejuvenation effect on the old hippocampal methylome, extending evidence that viral vector-mediated delivery of Yamanaka genes in the brain can have regenerative effects.

Xiaoting Dai, Xinghua Li, Scott Pletcher, David Paris, Leonid Kruglyak, Jacob Sobota, Longhua Guo

The research demonstrated that the sexually reproducing lineage of the planarian Schmidtea mediterranea, a freshwater species known for its remarkable regenerative capabilities, shows signs of aging. However, the process of amputation followed by regeneration reversed these aging signs, restoring youthful gene expression, stem cell states, tissue composition, and overall physiology. Findings suggest that planaria's natural age-reversal solution could offer valuable insights into anti-aging strategies for humans.

José V. V. Isola, Sarah R. Ocañas, Chase R. Hubbart, Sunghwan Ko, Samim Ali Mondal, Jessica D. Hense, Augusto Schneider, Susan Kovats, Willard M. Freeman, Michael B. Stout

Single-cell RNA sequencing was prformed on ovarian tissue from young and reproductively aged mice, revealing significant transcriptomic changes with aging. Notably, there was a doubling of immune cells, especially T and B lymphocytes, and changes in stromal fibroblasts pathways. The follicular cells exhibited increased stress response, immunogenic and fibrotic signaling with age, more in atretic granulosa cells, but also noticeable in healthy granulosa cells. Interestingly, no age-related cellular senescence was observed, raising new hypotheses for mechanisms of ovarian aging.

Patrick Treat Paine, Cheyenne Rechsteiner, Francesco Morandini, Gabriela Desdin Mico, Calida Mrabti, Alberto Parras, Amin Haghani, Robert Brooke, Steve Horvath, Andrei Seluanov, Vera Gorbunova, Alejandro Ocampo

The study examined the rejuvenating properties of cellular reprogramming in an accelerated aging mouse model. Through the process of in vivo partial cellular reprogramming, they found significant lifespan extension and restoration of aging phenotypes. Particularly, the technique effectively reversed DNA damage, stimulated DNA repair processes, and rejuvenated the epigenetic clock. Additionally, inhibiting TGFb pathway receptors produced similar benefits. The study suggests cellular reprogramming responds to aging signals and restores youthful molecular characteristics, offering potential breakthroughs in anti-aging research.