bims-minfam 2025-06-01 papers

Issue of 2025–06–01
four papers selected by
Ayesh Seneviratne, McMaster University

Nat Aging. 2025 May 28.

The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan.

Lisonia Gkioni, Tobias Nespital, Maarouf Baghdadi, Carolina Monzó, Jitin Bali, Taim Nassr, Anna Lena Cremer, Andreas Beyer, Joris Deelen, Heiko Backes, Sebastian Grönke, Linda Partridge.

Suppression of the insulin-IGF-mTORC1-Ras network ameliorates aging in animals. Many drugs have targets in the network because of its roles in cancer and metabolic disease and are candidates for repurposing as geroprotectors. Rapamycin, an established geroprotective drug, blocks mTORC1 signaling, and trametinib inhibits the Ras-MEK-ERK pathway. In this study, we assessed survival and health of male and female mice treated with trametinib, rapamycin or their combination. We show here that trametinib treatment extended lifespan in both sexes and that its combination with rapamycin was additive. Combination treatment reduced liver tumors in both sexes and spleen tumors in male mice, blocked the age-related increase in brain glucose uptake and strongly reduced inflammation in brain, kidney, spleen and muscle and circulating levels of pro-inflammatory cytokines. We conclude that trametinib is a geroprotector in mice and that its combination with rapamycin is more effective than either drug alone, making the combination a candidate for repurposing as a gerotherapy in humans.

DOI: https://doi.org/10.1038/s43587-025-00876-4

Clin Investig Arterioscler. 2025 May 23. pii: S0214-9168(25)00010-5. [Epub ahead of print] 500767

Myeloproliferative neoplasms: A model of the journey from clonal hematopoiesis to cardiovascular disease and cancer.

Santiago Redondo.

In the last decade, the coming of next-generation sequencing and its application to large human populations is breaking the barrier between inflammation and cancer. Indeed, acquired mutations in key genes that regulate hematopoiesis and thus confer a selective advantage in the proliferation of hematopoietic progenitors have established the concept of clonal hematopoiesis of indeterminate potential or CHIP. A growing body of clinical and experimental evidence is highlighting the link between CHIP and adverse outcomes, in particular atherosclerotic cardiovascular disease and cancer. The apparent surprise about how these two different entities share common mechanisms can be explained by myeloproliferation and inflammation. These mechanisms are involved not only in the development of myeloid tumors but also in atherogenesis. Myeloproliferative neoplasms or MPN are a type of myeloid tumors where thrombotic risk is increased not only by higher blood counts but also by means of an accelerated atherosclerosis. Therefore, myeloproliferative neoplasms are a model of the link between clonal hematopoiesis and atherosclerotic cardiovascular disease. The concept of CHIP has important clinical applications. A deeper understanding of these mechanisms may pave the way for the future early diagnosis and potential pre-emptive treatments of these two major causes of death.

Keywords: Aterosclerosis; Atherosclerosis; Autoimmunity; Autoinmunidad; Bone marrow; Cardio-Oncología; Cardio-oncology; Cardiovascular risk; Clonal hematopoiesis; Hematopoyesis clonal; Inflamación; Inflammation; Myeloproliferative neoplasm; Médula ósea; Neoplasias mieloproliferativas; Riesgo cardiovascular

DOI: https://doi.org/10.1016/j.arteri.2025.500767

Nat Aging. 2025 May 26.

Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK.

Arun Balachandran, Heming Pei, Yifan Shi, John R Beard, Avshalom Caspi, Alan A Cohen, Benjamin W Domingue, Claire Eckstein Indik, Luigi Ferrucci, Alex Furuya, Meeraj Kothari, Terrie E Moffitt, Calen P Ryan, Vegard Skirbekk, Yuan S Zhang, Daniel W Belsky.

As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy do not distinguish differences caused by early-life factors, like prenatal care and nutrition, from those caused by ongoing changes in people's bodies that are due to aging and that may be modifiable. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and populations in the speed of aging-related health declines. The adapted Pace of Aging method, implemented in parallel in data from the US Health and Retirement Study and in the English Longitudinal Study of Aging (combined n = 19,045), integrates longitudinal data on blood biomarkers, physical measurements and functional tests. It reveals stark differences in rates of aging between population subgroups and demonstrates strong and consistent prospective associations with incident morbidity, disability and mortality. This adapted and generalizable method to measure Pace of Aging can advance the population science of healthy longevity.

DOI: https://doi.org/10.1038/s43587-025-00866-6