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Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging

Johan Auwerx, Xiaoxu Li, Mario Romani, Tanes Imamura de Lima, Sandra Rodriguez Lopez, Hao Li, Martin Rainer Wohlwend, Pirkka-Pekka Untamo Laurila, Ludger Jan Elzuë Goeminne, Dohyun Park

Disruption of mitochondrial function and protein homeostasis plays a central role in aging. However, how these processes interact and what governs their failure in aging remain poorly understood. Here, we showed that cer- amide biosynthesis controls the de ...

AMER ASSOC ADVANCEMENT SCIENCE2023

Secondary structure of the human mitochondrial genome affects formation of deletions

Jacques Fellay, Konstantin Popadin

BackgroundAging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain ...

BMC2023

The THO complex counteracts TERRA R-loop-mediated telomere fragility in telomerase(+) cells and telomeric recombination in ALT(+) cells

Joachim Lingner, Rita Valador Fernandes

Telomeres are the nucleoprotein structures at the ends of linear chromosomes. Telomeres are transcribed into long non-coding Telomeric Repeat-Containing RNA (TERRA), whose functions rely on its ability to associate with telomeric chromatin. The conserved T ...

OXFORD UNIV PRESS2023

Analysis of the influence of errors in DNA-based image coding

Touradj Ebrahimi, Michela Testolina, Davi Nachtigall Lazzarotto

In the last decade, DNA has been increasingly investigated as an alternative medium for cold data storage, presenting several advantages over standard hard drives such as a higher density, longer lifespan and lower energy consumption. However, such coding ...

2023

TFIIH moonlighting at telomeres

Joachim Lingner, Galina Glousker

Although telomeres are essential for chromosome stability, they represent fragile structures in our genome. Telomere shortening occurs during aging in cells lacking telomerase due to the end replication problem. In addition, recent work uncovered that the ...

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT2022

In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging

Patrick Descombes, Jérome Feige, Sylviane Métairon, Omid Mashinchian, Filippo De Franceschi, Nicolas Bouche, Christophe Boss

Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specifi ...

2022

Reduced ech-6 expression attenuates fat-induced lifespan shortening in C. elegans

Richardus Houtkooper, Wen Gao, Yuan Liu

Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious e ...

Nature Portfolio2022

Identification and characterization of proteins that protect human telomeres from fragility

Anna Christina Näger

Difficulties to replicate telomeres - the ends of our chromosomes - can cause telomere shortening and genome instability. These difficulties are due to the repetitive DNA sequence and distinct structures at telomeres that challenge the semi-conservative DN ...

EPFL2022

V-ATPase/TORC1-mediated ATFS-1 translation directs mitochondrial UPR activation in C. elegans

Johan Auwerx, Kristina Schoonjans, Felix Naef, Xiaoxu Li, Jia Liu, Hao Li, Wen Gao, Nagammal Neelagandan, Yang Li, Amélia Lalou

To adapt mitochondrial function to the ever-changing intra- and extracellular environment, multiple mitochondrial stress response (MSR) pathways, including the mitochondrial unfolded protein response (UPRmt), have evolved. However, how the mitochondrial st ...

Rockefeller University Press2022

Mapping of Structure-Function Age-Related Connectivity Changes on Cognition Using Multimodal MRI

Dimitri Nestor Alice Van De Ville, Maria Giulia Preti

The relationship between age-related changes in brain structural connectivity (SC) and functional connectivity (FC) with cognition is not well understood. Furthermore, it is not clear whether cognition is represented via a similar spatial pattern of FC and ...

FRONTIERS MEDIA SA2022

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