The 18S rRNA methyltransferase DIMT-1 regulates lifespan in the germline later in life

M. Hafiz Rothi, Gautam Chandra Sarkar, Joseph Al Haddad, Wayne Mitchell, Kejun Ying, Nancy Pohl, Roberto G. Sotomayor-Mena, Julia Natale, Scarlett Dellacona, Vadim N. Gladyshev and Eric Lieberman Greer ()
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M. Hafiz Rothi: Harvard Medical School
Gautam Chandra Sarkar: Washington University School of Medicine
Joseph Al Haddad: Boston Children’s Hospital
Wayne Mitchell: Harvard Medical School
Kejun Ying: Harvard Medical School
Nancy Pohl: Harvard Medical School
Roberto G. Sotomayor-Mena: Harvard Medical School
Julia Natale: Boston Children’s Hospital
Scarlett Dellacona: Harvard Medical School
Vadim N. Gladyshev: Harvard Medical School
Eric Lieberman Greer: Harvard Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Specialized ribosomes help determine which proteins are synthesized, however, the influence of age on ribosome heterogeneity and whether dysregulation of this process drives organismal aging is unknown. Here we examined the role of ribosomal RNA (rRNA) methylation in maintaining appropriate translation as organisms age. In a directed RNAi screen, we identified 18S rRNA N6’-dimethyl adenosine (m6,2A) methyltransferase, dimt-1, as a regulator of C. elegans lifespan and stress resistance. We demonstrate that DIMT-1 functions in the germline after mid-life to regulate lifespan. Depletion of dimt-1 leads to selective translation of transcripts important for stress resistance and lifespan regulation in the C. elegans germline including the cytochrome P450 daf-9, which synthesizes a steroid that signals from the germline to the soma. dimt-1 induced lifespan extension is dependent on the daf-9 signaling pathway. Our findings highlight ribosome heterogeneity, and specific rRNA modifications, in maintaining appropriate translation later in life to promote healthy aging.

Date: 2025
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DOI: 10.1038/s41467-025-62323-7

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