This work was spearheaded by @mhafizrothi, @Gautam_Sarkaar, and Joseph Alhaddad, who were helped by Wayne Mitchell, @KejunYing , Nancy Pohl, Roberto Sotomayor-Mena, Julia Natale, Scarlett Dellacono and @gladyshev_lab . Thanks to all the authors! 8/8.

DAF-9 was previously shown by @AntebiLab to produce the signaling lipid dafachronic acid to signal from the germline to the soma to regulate lifespan. , . dimt-1 induced lifespan extension was dependent on this pathway 7/8.

We also found DIMT-1 regulates selective translation of stress resistance and lifespan regulating transcripts in the worm's germline but not in the muscle. One transcript which we identified as displaying differential ribosome occupancy was the cytochrome P450 enzyme DAF-9. 6/8.

We found that dimt-1 deficiency requires the TOR signaling pathway and an intact germline to extend lifespan. Using auxin-inducible degron tagged dimt-1 and tissue specific RNAi we found DIMT-1 functions in the worms' germline after mid-life to regulate organismal lifespan 5/8.

An RNAi screen identified that dimt-1 KD caused lifespan extension. We had previously shown that DIMT-1 is an 18S rRNA m62A methylase and that methylated rRNAs are transmitted to subsequent generations to drive intergenerational response to starvation 4/8.

We found DIMT-1 functions in the germline and works after mid-life to extend lifespan. This reveals a new layer of regulation of lifespan, which transcripts are selectively translated, and found that ribosome heterogeneity is critical later in life to promote healthy aging. 3/8.

As we age there is a dysregulation of which proteins are degraded, and which proteins are produced. We showed that DIMT-1 methylation of the ribosome selectively regulates the production of stress resistance and longevity regulating proteins and regulates aging. 2/8.

Excited to see our manuscript out @NatureComms We identified that the 18S rRNA methylase DIMT-1 regulates lifespan by functioning in the germline after midlife. 1/8.

Just began at @ericgreerlab.bsky.social.

Super proud of my mom, Judy Lieberman, and all she has done throughout her wonderful career!.

Happy to have helped contribute to this work with @YingZhang_Lab, @pouryany, Haiwei Zhang, @simonyuanwang, Zhouyihan Li, @bowen0324, Dian-Jang Lee, Zhibin Zhang, Athanasios Ploumakis, Ming Shi, @WuLabHarvard, @winhide, and Judy Lieberman! (18/18).

. immune danger signaling pathways, for example those encoding interferons or components of the necroptosis and pyroptosis machinery, contribute to the protective effect of decitabine (17/18).

. and co-expression of receptors and their ligands in the tumor and infiltrating cytotoxic lymphocytes was reduced, suggesting that their interactions were impaired. Knockdown of a panel of tumor genes in the melanoma implants indicated that genes involved in innate. (16/18).

Reduced tumor cell expression of type-I and type-II interferon pathway genes and interferon-stimulated genes during immunoediting and its restoration with decitabine was especially prominent. T cell exhaustion occurred rapidly in tumor-infiltrating lymphocytes, . (15/18).

Within the tumor, the number of NK and T lymphocytes (including memory CD8+ cells) increased, as did the expression of anti-tumor genes within them. Type 1 conventional dendritic cells also increased, and myeloid-derived suppressor cells almost disappeared after treatment (14/18).

Many key immune pathway genes were epigenetically repressed in late tumors and derepressed when late tumors were treated with decitabine. Decitabine treatment also strongly inhibited tumor growth. (13/18).

Changes in tumor gene expression from early to late tumors concentrated on the suppression of genes that promote tumor recognition by innate and adaptive immune cells, rather than on changes in the expression of genes that promote tumor-cell-intrinsic malignancy (Fig. 1b) 12/18.

breast cancer or melanoma implants, with the DNA methyltransferase inhibitor decitabine and measuring tumor growth and immune cell infiltration. (11/18).

and to capture changes in the numbers and properties of infiltrating immune cells. Further, we used decitabine to measure the effects of DNA methylation inhibition on tumor immunoediting in mice with Her2-driven inducible breast cancer, and mice with triple negative. (10/18).

We performed scRNA-seq of tumor tissue harvested one week and one month after Her2 oncogene induction to characterize ‘early��� and ‘late’ tumors, respectively (Fig 1a). Bioinformatic analysis was used to identify key pathways in which gene expression changed significantly, (9/18)