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Study · Animal study (in vivo) · mouse · 2023

2 results

The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging.

Sanchez-Contreras M, Sweetwyne MT, Tsantilas KA, Whitson JA, Campbell MD, Kohrn BF, Kim HJ, Hipp MJ, Fredrickson J, Nguyen MM, Hurley JB, Marcinek DJ, Rabinovitch PS, Kennedy SR

eLife17 Feb 2023Cited by 67 (Europe PMC)

PMID36799304 (opens in a new tab)PMCIDPMC10072880 (opens in a new tab)DOI10.7554/elife.83395 (opens in a new tab)PepBankPUB-36799304
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Summary

Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism of mitochondrial and tissue dysfunction that occurs during aging. A thorough characterization of age-associated mtDNA somatic mutations has been hampered by the limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function. G→A/C→T substitutions, indicative of replication errors and/or cytidine deamination, were the predominant mutation type across all tissues and increased with age, whereas G→T/C→A substitutions, indicative of oxidative damage, were the second most common mutation type, but did not increase with age regardless of tissue. We also show that clonal expansions of mtDNA mutations with age is tissue- and mutation type-dependent. Unexpectedly, mutations associated with oxidative damage rarely formed clones in any tissue and were significantly reduced in the hearts and kidneys of aged mice treated at late age with elamipretide or nicotinamide mononucleotide. Thus, the lack of accumulation of oxidative damage-linked mutations with age suggests a life-long dynamic clearance of either the oxidative lesions or mtDNA genomes harboring oxidative damage.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In aged mice treated at late age, elamipretide significantly reduced mutations associated with oxidative damage in the heart.

    In plain wordsIn aged mice, elamipretide given late in life reduced oxidative-damage-type mutations in mitochondrial DNA of the heart.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseOxidative damage-associated mtDNA mutations in the heart
    Study

    mousen: not reported in source

    Aged mice treated at late age
    Outcome group
    Aging markers · Aging and longevity
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Unexpectedly, mutations associated with oxidative damage rarely formed clones in any tissue and were significantly reduced in the hearts and kidneys of aged mice treated at late age with elamipretide or nicotinamide mononucleotide.
    1 context sentence
    Summary · context
    Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In aged mice treated at late age, elamipretide significantly reduced mutations associated with oxidative damage in the kidney.

    In plain wordsIn aged mice, elamipretide given late in life reduced oxidative-damage-type mutations in mitochondrial DNA of the kidney.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseOxidative damage-associated mtDNA mutations in the kidney
    Study

    mousen: not reported in source

    Aged mice treated at late age
    Outcome group
    Aging markers · Aging and longevity
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Unexpectedly, mutations associated with oxidative damage rarely formed clones in any tissue and were significantly reduced in the hearts and kidneys of aged mice treated at late age with elamipretide or nicotinamide mononucleotide.
    1 context sentence
    Summary · context
    Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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