Spermidine Feeding Decreases Age-Related Locomotor Activity Loss and Induces Changes in Lipid Composition

Minois, Nadège; Rockenfeller, Patrick; Smith, Terry; Carmona-Gutiérrez, Didac

doi:10.1371/journal.pone.0102435

Cited by 45 publications

(30 citation statements)

References 67 publications

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“…Importantly, our results suggest an increased GSH turnover and spermidine synthesis in muscle of UCP1‐TG mice, consistent with increased endogenous antioxidant defense enzyme activity as observed previously (51). Interestingly, spermidine was recently related to enhanced oxidative stress protection (75) and prevention of age‐related locomotor activity loss (76). Whether muscle mitochondrial distress‐induced ROS production is the cause for the metabolic programming remains to be elucidated in future studies.…”

Section: Discussionmentioning

confidence: 99%

Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux

et al. 2014

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Recent studies on mouse and human skeletal muscle (SM) demonstrated the important link between mitochondrial function and the cellular metabolic adaptation. To identify key compensatory molecular mechanisms in response to chronic mitochondrial distress, we analyzed mice with ectopic SM respiratory uncoupling in uncoupling protein 1 transgenic (UCP1-TG) mice as model of muscle-specific compromised mitochondrial function. Here we describe a detailed metabolic reprogramming profile associated with mitochondrial perturbations in SM, triggering an increased protein turnover and amino acid metabolism with induced biosynthetic serine/ 1-carbon/glycine pathway and the longevity-promoting polyamine spermidine as well as the trans-sulfuration pathway. This is related to an induction of NADPHgenerating pathways and glutathione metabolism as an adaptive mitohormetic response and defense against increased oxidative stress. Strikingly, consistent muscle retrograde signaling profiles were observed in acute stress states such as muscle cell starvation and lipid overload, muscle regeneration, and heart muscle inflammation, but not in response to exercise. We provide conclusive evidence for a key compensatory stresssignaling network that preserves cellular function, oxidative stress tolerance, and survival during conditions of increased SM mitochondrial distress, a metabolic reprogramming profile so far only demonstrated for cancer cells and heart muscle.-Ost, M., Keipert, S., van Schothorst, E. M., Donner, V., van der Stelt, I., Kipp, A. P., Petzke, K.-J., Jove, M., Pamplona, R., Portero-Otin, M., Keijer, J., Klaus, S. Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux. FASEB J. 29, 1314-1328 (2015). www.fasebj.org Key Words: amino acid metabolism • metabolic reprogramming • mitochondrial myopathy • oxidative stress tolerance • polyamines SKELETAL MUSCLE (SM) WASTING, or atrophy, occurs as a physiologic response to muscle disuse, fasting, starvation, and aging; it also occurs in a wide range of systemic diseases, including cancer, denervation, and diabetes mellitus (1-4). Numerous studies connected alterations in mitochondrial function to muscle atrophy, focusing on mitochondrial respiratory chain dysfunction or formation of reactive oxygen species (ROS) (5), as mitochondria represent an important site of cellular ROS production (6). Mitochondria are key dynamic organelles that not only provide ATP via oxidative phosphorylation but also are involved in the cellular integrated stress response (7) and in mitohormesis, a molecular adaptation and retrograde response resulting in stress resistance (8).We previously demonstrated in a transgenic mouse model with alterations in SM mitochondrial function (uncoupling protein 1 [UCP1] transgenic [TG] mice [UCP1-TG], with ectopic expression of UCP1 in SM) an elevated endogenous antioxidant defense system, induced integrated stress response but also compromised mitochondrial respiratory chain capacity (9) and a strong reduction in SM mass (10). In contrast...

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Section: Discussionmentioning

confidence: 99%

Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux

et al. 2014

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“…Mice with liver-specific overexpression of TFEB were rescued from dietary-induced obesity and metabolic syndrome, but only when autophagy was functional (85). Interestingly, recent evidence from studies in D. melanogaster suggests that spermidine treatment alters organismal lipid profiles in an autophagy-dependent manner (86). It remains to be investigated whether a nonspecific change in lipid flux or selective modulation of some lipid species, e.g., by shifting saturation states (87), contributes to the beneficial effects of autophagy.…”

Section: Autophagy Induction Suffices To Promote Longevitymentioning

confidence: 99%

Essential role for autophagy in life span extension

Madeo¹,

Zimmermann²,

Maiuri³

et al. 2015

J. Clin. Invest.

383

289

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Life and health span can be prolonged by calorie limitation or by pharmacologic agents that mimic the effects of caloric restriction. Both starvation and the genetic inactivation of nutrient signaling converge on the induction of autophagy, a cytoplasmic recycling process that counteracts the age-associated accumulation of damaged organelles and proteins as it improves the metabolic fitness of cells. Here we review experimental findings indicating that inhibition of the major nutrient and growth-related signaling pathways as well as the upregulation of anti-aging pathways mediate life span extension via the induction of autophagy. Furthermore, we discuss mounting evidence suggesting that autophagy is not only necessary but, at least in some cases, also sufficient for increasing longevity

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“…The essential mechanistic role of lipid metabolism and transport in defining longevity of this unicellular eukaryote further supports the notion that some aspects of the maintenance of lipid homeostasis are essential for healthy aging in evolutionarily distant organisms. These eukaryotic organisms include not only laboratory strains of budding yeast, roundworms (15,, fruit flies (214)(215)(216)(217)(218)(219)(220)(221)(222)(223) and mammals (208,(224)(225)(226)(227)(228)(229)(230)(231)(232)(233)(234)(235)(236)(237)(238)(239)(240)(241), but also humans (208,(232)(233)(234)(235)(241)(242)(243)(244)(245)(246). The major challenge now is to get a greater insight into the mechanisms through which lipid metabolism and transport define lifespan and healthspan in multicellular model organisms and humans.…”

Section: Summary and Perspectivementioning

confidence: 99%

Lipid metabolism and transport define longevity of the yeast Saccharomyces cerevisiae

et al. 2018

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Emergent evidence indicates that certain aspects of lipid synthesis, degradation and interorganellar transport play essential roles in modulating the pace of cellular aging in the budding yeast Saccharomyces cerevisiae. The molecular mechanisms underlying the vital roles of lipid metabolism and transport in defining yeast longevity have begun to emerge. The scope of this review is to critically analyze recent progress in understanding such mechanisms.

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Spermidine Feeding Decreases Age-Related Locomotor Activity Loss and Induces Changes in Lipid Composition

Cited by 45 publications

References 67 publications

Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux

Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux

Essential role for autophagy in life span extension

Lipid metabolism and transport define longevity of the yeast Saccharomyces cerevisiae

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