Cancer and aging

Aging-related immune alteration has been attributed to increased susceptibility to infection and cancer. Here the authors show, using both lung cancer samples and mouse models, that aged Treg cells express higher levels of an ER enzyme, SOAT2, have altered cholesterol metabolism, and induce CD8⁺ T cell senescence to dampen anti-tumor immunity.

Telomere maintenance by telomerase depends on the correct assembly and the recruitment of the enzyme complex. Here, the authors reveal that the RNA/DNA binding proteins NONO, SFPQ, and PSPC1 interact with telomerase via the hTR RNA template, facilitating telomerase trafficking out of Cajal bodies and recruitment to the telomere.

Cancer is known to increase biological age compared with non-cancer people of the same age. Here, the authors confirm greater biological age among cancer survivors using multiple aging constructs, and a strong association with mortality.

Cancer incidence is rare in long-lived bats. Here the authors find that although bat fibroblasts express telomerase and require only two oncogenic hits for malignant transformation, bats may rely on elevated p53 signaling and enhanced immunosurveillance to prevent cancer.

Acetylome and proteome data analysis across 107 mammalian species identifies significant longevity-associated acetylated lysines. This study proposes a link between protein acetylation conservation and changes in mammalian longevity during evolution.

The aging immune system is characterized by changes in immune cell frequencies and functionality. Here the authors report dynamics of age-related divergence of circulating immune responses in patients with solid tumors treated with immune checkpoint inhibitors

Cheng et al. explore the impact of trimetazidine, an anti-ischemic agent that preferentially potentiates cellular glucose oxidation, on cancer risk. Findings show an association of use with a reduced long-term risk of malignancies.

Aging is a risk factor of cancer, but how an aged immune system transforms the tumor microenvironment (TME) is unclear. By leveraging scRNA-seq analysis in a mouse model of metastatic melanoma, here the authors show that a γδ17-dependent increase in neutrophils inhibits the proliferation and stemness of CD8⁺ T cells, thereby promoting tumor metastasis.

Herzog et al. dissect functionally enriched groups of CpG associated with cellular senescence, proliferation and aging. Some non-cancer tissues from breast cancer patients show younger epigenetic ages than in controls, while breast cancer tissue looks generally older, providing evidence for discordant systemic aging in breast cancer.

Our study highlights the decline of UPF1, a key component of nonsense-mediated mRNA decay (NMD), during cellular senescence and its impact on NMD efficiency, leading to the accumulation of aberrant mRNAs.

Chen et al. generate mimicking dormant clinical anti-estrogen-induced estrogen receptor positive mammary carcinoma (ER+MC) models. TFF3 is identified as a prognostic indicator and epigenetically regulated oncogenic driver of anti-estrogen-induced dormancy in ER+MC with combined inhibition of TFF3 and CDK4/6 exhibiting potential to ameliorate outcomes in anti-estrogen-induced ER+MC.

Mendelian randomization identifies cellular senescence-related genes that are causally associated with multiple tumors and additional analyses explore their possible mechanisms and clinical value.

Aging is a risk factor for blood malignancies, leading to increased myelopoiesis and impaired immunity. Here, the authors show that aging alters cellular and molecular properties of HSC subsets, with changes starting as early as the juvenile stage.

The heterodimer of METTL1-WDR4 is responsible for adding methylation group to the N7 atom of guanine (m7G) in tRNA molecules. Here the authors show how the tRNA m7G modification mediates tRNA stability to control proteostasis by maintaining efficient protein synthesis, which is important for preventing premature senescence 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.

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.