| Title: | Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging |
| Journal: | Nature Communications |
| Published: | 18 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42000749/ |
| DOI: | https://doi.org/10.1038/s41467-026-71508-7 |
Publication 17946
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Abstract
Mitochondrial dysfunction is a prominent hallmark of aging contributing to the decline of metabolic plasticity in late life. While genetic distortions of mitochondrial integrity elicit premature aging, the mechanisms leading to "natural" aging of mitochondria are less clear. Here we use proteomics, lipidomics, genetics and functional tests in wild type Caenorhabditis elegans and long-lived clk-1(qm30) and isp-1(qm150) mitochondrial mutants to identify molecular pathways that support longevity amid persistent mitochondrial inefficiency. These tests and subsequent transcriptomics and metabolomics analyses in humans reveal aging-associated decline of phosphatidylcholine synthesis as a trigger of mitochondrial network disruption, which contributes to mitochondrial dysfunction during normal aging. Moreover, ectopic boosting of phosphatidylcholine levels via diet restores late life mitochondrial integrity in vivo in nematodes and reinstates metabolic resilience in human cell culture tests. We thus describe a previously unrecognized natural driver of mitochondrial decline in aging that is malleable by dietary interventions.</p>
12 Keywords
- Aging
- Animals
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Choline Kinase
- Humans
- Longevity
- Metabolomics
- Mitochondria
- Mutation
- Phosphatidylcholines
- Proteomics
13 Authors
- Tetiana Poliezhaieva
- Yuting Li
- Prerana Shrikant Chaudhari
- Ulas Isildak
- Pol Alonso-Pernas
- Isabela Santos Valentim
- Fengting Su
- Lilia Espada
- Melike Bayar
- Li Fu
- Andreas Koeberle
- Handan Melike Dönertaş
- Maria A. Ermolaeva
1 Application
| Application ID | Title |
|---|---|
| 129228 | Drivers and Consequences of Immunosenescence and Inflammaging in Humans |
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