Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging.
Poliezhaieva, T.; Pernas, P. A.; Espada, L.; Bayar, M.; Li, Y.; Donertas, H. M.; Ermolaeva, M.
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Mitochondrial dysfunction is a prominent hallmark of aging contributing to the functional 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 initially used proteomics, genetics and functional tests in wild type C. elegans and long-lived clk-1(qm30) and isp-1(qm150) mitochondrial mutants to identify molecular pathways that safeguard longevity amid persistent mitochondrial inefficiency. Strikingly, these analyses and subsequent transcriptomic and functional tests in the human system revealed aging-associated decline of phosphatidylcholine (PC) synthesis as a trigger of mitochondrial network disruption, which contributes to mitochondrial dysfunction during normal aging. Moreover, we found that ectopic boosting of PC levels via diet restores late life mitochondrial integrity in vivo and rescues metabolic plasticity in cell culture tests. Our work thus uncovered a novel natural driver of mitochondrial aging that is malleable by dietary interventions.
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