Publications by Tanes Imamura de Lima

A lysosomal surveillance response to stress extends healthspan

Johan Auwerx, Yang Li, Wen Gao, Xiaoxu Li, Amélia Lalou, Tanes Imamura de Lima, Qi Wang, Jia Liu

Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal ...

Springer Science and Business Media LLC2025

Cyclo His-Pro Attenuates Muscle Degeneration in Murine Myopathy Models

Johan Auwerx, Xiaoxu Li, Alessia De Masi, Tanes Imamura de Lima, Keno Strotjohann

Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progress ...

Wiley2024

Safe and Orally Bioavailable Inhibitor of Serine Palmitoyltransferase Improves Age-Related Sarcopenia

Johan Auwerx, Jean-David Horacio Morel, Alessia De Masi, Tanes Imamura de Lima, Sandra Rodriguez Lopez

The accumulation of ceramides and related metabolites has emerged as a pivotal mechanism contributing to the onset of age-related diseases. However, small molecule inhibitors targeting the ceramide de novo synthesis pathway for clinical use are currently u ...

2024

Inhibition of CERS1 in skeletal muscle exacerbates age-related muscle dysfunction

Olivier Burri, Johan Auwerx, Giacomo Vincenzo Giorgio Von Alvensleben, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Xiaoxu Li, Ludger Jan Elzuë Goeminne, Amélia Lalou, Tanes Imamura de Lima, Barbara Moreira Crisol, Renata Mangione

Age-related muscle wasting and dysfunction render the elderly population vulnerable and incapacitated, while underlying mechanisms are poorly understood. Here, we implicate the CERS1 enzyme of the de novo sphingolipid synthesis pathway in the pathogenesis ...

2023

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

Johan Auwerx, Hao Li, Mario Romani, Dohyun Park, Pirkka-Pekka Untamo Laurila, Changmyung Oh, Martin Rainer Wohlwend, Jean-David Horacio Morel, Xiaoxu Li, Ludger Jan Elzuë Goeminne, Tanes Imamura de Lima, Sandra Rodriguez Lopez, Barbara Moreira Crisol

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

Sphingolipids accumulate in aged muscle, and their reduction counteracts sarcopenia

Johan Auwerx, Maroun Bou Sleiman, Peiling Luan, Davide D'Amico, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Sébastien Robert Victor Herzig, Tanes Imamura de Lima, Qi Wang, Barbara Moreira Crisol

Age-related muscle dysfunction and sarcopenia are major causes of physical incapacitation in older adults and currently lack viable treatment strategies. Here we find that sphingolipids accumulate in mouse skeletal muscle upon aging and that both genetic a ...

2022

Inhibition of sphingolipid de novo synthesis counteracts muscular dystrophy

Johan Auwerx, Peiling Luan, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Ludger Jan Elzuë Goeminne, Tanes Imamura de Lima

Duchenne muscular dystrophy (DMD), the most common muscular dystrophy, is a severe muscle disorder, causing muscle weakness, loss of independence, and premature death. Here, we establish the link between sphingolipids and muscular dystrophy. Transcripts of ...

2022

Pleiotropic effects of mitochondria in aging

Johan Auwerx, Adrienne Joëlle Laurence Mottis, Yang Li, Tanes Imamura de Lima

Aging is typified by a progressive decline in mitochondrial activity and stress resilience. Here, we review how mitochondrial stress pathways have pleiotropic effects on cellular and systemic homeostasis, which can comprise protective or detrimental respon ...

SPRINGERNATURE2022

The exercise-induced long noncoding RNA CYTOR promotes fast-twitch myogenesis in aging

Johan Auwerx, Mario Romani, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Tanes Imamura de Lima

Skeletal muscle displays remarkable plasticity upon exercise and is also one of the organs most affected by aging. Despite robust evidence that aging is associated with loss of fast-twitch (type II) muscle fibers, the underlying mechanisms remain to be elu ...

2021

Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy

Johan Auwerx, Pénélope Andreux, Peiling Luan, Hao Li, Davide D'Amico, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Tanes Imamura de Lima

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, and despite advances in genetic and pharmacological disease-modifying treatments, its management remains a major challenge. Mitochondrial dysfunction contributes to DMD, yet the mecha ...

AMER ASSOC ADVANCEMENT SCIENCE2021

Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity

Johan Auwerx, Umberto De Marchi, Tanes Imamura de Lima

Sustained ryanodine receptor (RyR) Ca2+ leak is associated with pathological conditions such as heart failure or skeletal muscle weakness. We report that a single session of sprint interval training (SIT), but not of moderate intensity continuous training ...

Nature Portfolio2021

NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle

Johan Auwerx, Hongbo Zhang, Hao Li, Vincenzo Sorrentino, Mario Romani, Changmyung Oh, Tanes Imamura de Lima

Aging is characterized by loss of proteostasis and mitochondrial homeostasis. Here, we provide bioinformatic evidence of dysregulation of mitochondrial and proteostasis pathways in muscle aging and diseases. Moreover, we show accumulation of amyloid-like d ...

2021

Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression

Johan Auwerx, Tanes Imamura de Lima

MicroRNAs (miRNAs) have been implicated in oxidative metabolism and brown/beige adipocyte identity. Here, we tested whether widespread changes in miRNA expression promoted by treatment with the small-molecule enoxacin cause browning and prevent obesity. En ...

AMER ASSOC ADVANCEMENT SCIENCE2020

Opposing action of NCoR1 and PGC-1 alpha in mitochondrial redox homeostasis

Johan Auwerx, Adrienne Joëlle Laurence Mottis, Tanes Imamura de Lima

The ability to respond to fluctuations of reactive oxygen species (ROS) within the cell is a central aspect of mammalian physiology. This dynamic process depends on the coordinated action of transcriptional factors to promote the expression of genes encodi ...

ELSEVIER SCIENCE INC2019