Cancer and aging

Meguro et al. show an accumulation of p16^high senescent fibroblasts in the aging bladder that serves as a cancer-permissive niche and promotes tumor growth by secreting CXCL12. Inhibition of senescence or CXCL12 signaling suppresses bladder tumor growth.

Castro, Shindyapina et al. explore how aging promotes B cell lymphoma in mice, identifying a population of age-associated clonal B cells that expands through mutation, c-Myc activation and epigenetic alterations to drive age-associated malignancy.

The authors show that Hog1, the ortholog of mammalian p38 MAPK, is activated during replicative senescence to counteract the increased ROS levels independently of the checkpoint pathway in telomerase-negative Saccharomyces cerevisiae cells.

DNA methylation (DNAm) clocks can track mitotic age, but their potential use for cancer risk prediction remains less explored. Here, the authors develop a DNAm counter of total mitotic age (stemTOC) that shows an increase of mitotic age in normal tissues and precancerous lesions.

Aging-related cancer incidence remains not fully understood. Here, the authors depict a progressive process of senescence in murine mammary stem cells at single-cell resolution, which is governed by the transcription factor Bcl11b and associated with enhanced chemical-induced tumorigenesis in aged mice.

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.

A study of 4,645 children in four countries in East Africa, 800 with Burkitt lymphoma (BL), identifies an association between HLA-DQA1*04:01 and variant rs2040406(G) and elevated risk of BL in Africa.

Natural Killer (NK) cells play a role in suppressing the development of certain subtypes of acute myeloid leukemia as shown by employing Rag2^−/− mice as model system, which lack functional lymphocytes but have hyperactive NK cells.

The progranulin-derived synthetic protein Atsttrin affects osteoclastogenesis and osteoblastogenesis via the TNFR signaling pathway, suggesting that this protein could potentially be used to treat inflammation-related bone diseases like osteoporosis.

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.