iiinova — where your digital self keeps evolving

Marta Grońska-Pęski @gronskapeski.bsky.social · 30/09/2026

It was a pleasure to present my work at the CHGG retreat and be honored for the best postdoc poster.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 09/09/2026

Most importantly, huge thanks to my mentor Gilad Evrony, and to Dr. Jonathan Shoag and @asrinivasa.bsky.social for working with me on this. And I’m so grateful to @vickyar.bsky.social , Dr. Joseph Takahashi, and Dr. Carla Green who created this cohort of mice and generously collaborated with us.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 09/09/2026

Surprisingly, we found that CR’s effect was not uniform across the genome: in some tissues, mutation reductions were greatest in transcriptionally inactive regions.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 09/09/2026

CR also reduced indel burdens in liver, hepatocytes, and cerebellar neurons.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 09/09/2026

Using high-fidelity duplex sequencing (NanoSeq), we found that CR reduced somatic mutation burdens vs. ad libitum (AL) feeding across multiple tissues & cell types. Liver, kidney, and hepatocytes had lower substitution burdens, and the effect varied by tissue and cell type.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 09/09/2026

Can dietary interventions change how fast genomes accumulate mutations with age? We studied how caloric restriction (CR)—one of the most robust lifespan-extending interventions—affects somatic mutations across the genome in different tissues and cell types in mice.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 09/09/2026

Surprisingly, we found that CR’s effect was not uniform across the genome: in some tissues, mutation reductions were greatest in transcriptionally inactive regions.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 09/09/2026

CR also reduced indel burdens in liver, hepatocytes, and cerebellar neurons.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 09/09/2026

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

Thank you also to Pew Trusts, @NIH, SMaHT Network, and the Jacob Goldfield Foundation for funding, and to the generous donations of individuals to the NIH NeuroBiobank and University of Florida Neuro Genetics repositories with support from National Ataxia Foundation.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

Grateful to my mentor @giladevrony for his guidance and support and @Amoolya1199 for her contributions.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

See our paper for more details and additional analyses of mutagenesis in cerebellar ataxia neurodegeneration syndromes. authors.elsevier.com/a/a1nan83Btf...

authors.elsevier.com

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

Overall, neuronal identity shapes somatic mutation in unexpected ways. Substitutions, especially SBS5, are surprisingly similar across cell types, while transcription is linked to most differences. Profiling more cell types may reveal mechanisms shaping genome integrity with age.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

As transcriptional activity of genomic regions increased, PN and GN substitution rates changed in opposite directions. The transcription effect was even stronger for PN indels.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

Although their substitution rates were similar, PNs and GNs differed slightly in substitution patterns and SBS1/SBS16 mutational signature activity. Yet the dominant aging signature, SBS5, was similar in PNs and GNs, constraining hypotheses about its origins in these neurons.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

Surprisingly, both types of neurons accumulated substitution mutations at the same rates! On the other hand, PNs accumulated indels at approximately twice the rate of GNs.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

The striking differences in PN and GN size, metabolism, and electrical activity made them a great test case for how cell biology shapes somatic mutations. We isolated PNs and GNs postmortem across the lifespan, followed by high-fidelity duplex DNA sequencing (NanoSeq).

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

Do very different types of neurons differ in their rates and patterns of somatic mutation? We profiled somatic mutations in human cerebellar Purkinje neurons (PNs), one of the largest cells in the body, and granule neurons (GNs), one of the smallest.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

As transcriptional activity of genomic regions increased, PN and GN substitution rates changed in opposite directions. The transcription effect was even stronger for PN indels.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

Surprisingly, both types of neurons accumulated substitution mutations at the same rates! On the other hand, PNs accumulated indels at approximately twice the rate of GNs.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/08/2026

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Marta Grońska-Pęski @gronskapeski.bsky.social · 16/05/2026

Cooper you will always have my heart. ❤️ I will miss you.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 14/03/2026

Minnewaska hike with some lovely views.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 10/03/2026

Cooper is fed up with the MTA. Morning commute issues, afternoon commute train rerouted back to Manhattan. 2 hours later still not home.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 07/03/2026

This pair of ravens was like a pair of humans. If they could speak I’m sure they would have many tales to tell.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 07/03/2026

Flying across United Stats with clear skies leaves you with breathtaking views.

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Marta Grońska-Pęski @gronskapeski.bsky.social · 07/03/2026

It was a pleasure to present my work at the DNA, mutations, and cancer Gordon Conference in Ventura, CA. Amazing people and great science set in a beautiful place. #GordonConference #Ventura