Cancer and aging

It has been reported that the circadian clock regulator Bmal1 can modulate tumorigenesis. Here the authors show that ectopic expression of Bmal1 promotes an immune resistant mesenchymal melanoma cell state associated with increased AP-1 activity.

Here the authors find that erythroblasts of myelodysplastic syndromes with SF3B1 mutation leading to inefficient erythropoiesis show DNA replication stress with accelerated forks and reduced R-loops. Restoring R-loops by a histone deacetylase inhibitor rescues erythroid differentiation.

Bats have been suggested to be resistant to cancer due to mechanisms related to their evolved longevity, but the associated molecular drivers are still understudied. Here, the authors examine cancer resistance mechanisms across seven bat species using in vitro and in vivo models, and identify HIF1A, COPS5, and RPS3 as related genes.

Wang et al. generate a single nucleus-resolved transcriptomic atlas of primate adrenal aging, with which they demonstrate regional changes in adrenal aging, and establish the role of LDLR in impeding cholesterol uptake and DHEA-S production in aging.

Older age is associated with worse outcomes for patients with melanoma, and the underlying mechanisms are incompletely understood. Here the authors show that the loss of HAPLN1 in aged skin fibroblasts drives melanoma progression by increasing ICAM1 and angiogenesis. Blocking ICAM1 shrinks tumors, suggesting potential for age-specific melanoma therapy.

Using a multi-omics approach, Wang et al. explored sex-specific and region-specific patterns of intestinal aging in non-human primates, identifying regulators with conserved functions in Caenorhabditis elegans intestinal aging, in colitis in mice and in patient colorectal cancer samples.

The mechanisms underlying the influence of aging on cancer are incompletely understood. Warde et al. establish a new model of age- and sex-dependent adrenal cancer. Their work uncovers a tumor-protective role for myeloid immune cells that is enhanced by androgens.

Age related accumulation of adipocytes in the bone marrow could alter normal and leukemic haematopoiesis. Here, in fatty bone marrow (FBM) preclinical models, the authors show that inflammatory cytokines increased in the FBM, such as IL-6, promote DNMT3a driven clonal hematopoiesis.

Recent reports in oncological and non-oncological experimental setups provide strong evidence that senescent cells are under the surveillance of CD8 T cell-mediated adaptive immunity. These new data also shed light on the mechanisms that sensitize senescent cells to CD8 T cell-dependent killing, as well as those that enable senescent cells to evade CD8 T cell immunosurveillance. Understanding the interplay between cellular senescence and the adaptive immune system may open new strategies to ameliorate aging and aging-associated diseases.

The levels of catalytic subunit of the RNaseH2 enzyme, RNAseH2A, decrease during senescence promoting nucleotide accumulation and a senescence-associated secretory phenotype.

Methylmalonic acid (MMA) is increased in aging as well as produced by advanced tumors, and can drive pro-aggressive changes in these tumor cells. Here, the authors show that MMA can also act on fibroblasts in the tumor microenvironment, recruiting and activating them to further support tumor progression.

In human and murine GBM cells, and wildtype murine astrocytes, radiation induces senescence. Overall, female cells are more sensitive to radiation and to p21-induced senescence. This may contribute to the female survival advantage in GBM.

Ras mutations induce cell competition and cellular senescence to inhibit the proliferation of oncogenic mutated cells. Here the authors demonstrate that cellular senescence inhibits cell competition-induced elimination of oncogenic cells through HGF signalling.