Spermidine boosts autophagy to protect from synapse aging

Bhukel, Anuradha; Madeo, Frank; Sigrist, Stephan J.

doi:10.1080/15548627.2016.1265193

Cited by 52 publications

(41 citation statements)

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“…It has been confirmed that Spd inhibits cell senescence induced by neuroinflammation and oxidative stress in striatum 36 and protects against aging-induced synaptic senescence. 15,37,38 These previous findings offered a reasonable explanation for the results obtained in the present study. Furthermore, the present work demonstrated that Spd also overcame HG-induced neurotoxicity in HT-22 cells.…”

Section: Discussionsupporting

confidence: 92%

“…These results indicated that Spd is able to suppress HG‐induced senescence in HT‐22 cells. It has been confirmed that Spd inhibits cell senescence induced by neuroinflammation and oxidative stress in striatum and protects against aging‐induced synaptic senescence . These previous findings offered a reasonable explanation for the results obtained in the present study.…”

Section: Discussionsupporting

confidence: 91%

“…It has been found that the concentration of Spd is decreased with age in human cells, indicating Spd is associated with senescence . In addition, Spd can provide protection against the process of senescence in the heart, skeletal muscle and brain of mice. Furthermore, it has been confirmed that Spd obviously extend the lifespan of yeast, flies and worms, and human immune cells .…”

Section: Introductionmentioning

confidence: 99%

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Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Zhu

Fan

Tang

et al. 2018

Clin Exp Pharma Physio

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Hyperglycaemia-induced neurotoxicity involved in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglyceamic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti-aging function in many tissues. However, the role of Spd in hyperglyceamia-induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)-treated HT-22 cell as vitro model to investigate whether Spd protects neurons against hyperglyceamia-induced senescence and the mediatory role of CB1 receptor. The HT-22 cells were cultured in HG condition in the presence of different dose of Spd. Then, the viability of cells was measured by Cell Counting Kit-8 (CCK-8) assay. The senescence of cells was detected by Senescence-associated β-galactosidase (SA-β-Gal) staining. The expressions of p16 , p21 and CB1 receptor were measured by western blot. We found that Spd inhibited HG-induced neurotoxicity (the loss of cell viability) and senescence (the increase of SA-β-Gal positive cells, the upregulation of p16 and p21 ) in HT-22 cells. Also, Spd prevented HG-induced downregulation of CB1 receptor in HT-22 cells. Furthermore, we demonstrated that AM251 (a specific inhibitor of the CB1 receptor) reversed the protective effects of Spd on HG-induced neurotoxicity and senescence. These results indicated that Spd prevents HG-induced neurotoxicity and senescence via the upregulation of CB1 receptor. Our findings provide a promising future of Spd-based preventions and therapies for diabetic encephalopathy.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Zhu

Fan

Tang

et al. 2018

Clin Exp Pharma Physio

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“…Hence, in contrast to previous indications , these findings collectively suggest the importance of this highly unique post‐translational modification. Remarkably, spermidine, which is the donor for hypusination, is also well characterized as an autophagy inducer . Yet, it remains unknown whether spermidine‐induced autophagy can, to some extent, be attributed to activation of eIF5A via hypusination.…”

Section: Discussionmentioning

confidence: 99%

eIF 5A is required for autophagy by mediating ATG 3 translation

et al. 2018

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Autophagy is an essential catabolic process responsible for recycling of intracellular material and preserving cellular fidelity. Key to the autophagy pathway is the ubiquitin-like conjugation system mediating lipidation of Atg8 proteins and their anchoring to autophagosomal membranes. While regulation of autophagy has been characterized at the level of transcription, protein interactions and post-translational modifications, its translational regulation remains elusive. Here we describe a role for the conserved eukaryotic translation initiation factor 5A (eIF5A) in autophagy. Identified from a high-throughput screen, we find that eIF5A is required for lipidation of LC3B and its paralogs and promotes autophagosome formation. This feature is evolutionarily conserved and results from the translation of the E2-like ATG3 protein. Mechanistically, we identify an amino acid motif in ATG3 causing eIF5A dependency for its efficient translation. Our study identifies eIF5A as a key requirement for autophagosome formation and demonstrates the importance of translation in mediating efficient autophagy.

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“…Similarly, spermidine, a natural inducor of autophagy, maintains long‐lasting immunity and slows down progression of neurodegenerative diseases associated with age. These autophagy‐dependent effects are dependent on Atg7 gene function (Puleston et al ., ; Bhukel et al ., ). All this evidence supports the assertion that autophagy is involved in longevity, aging and development of age‐associated pathologies and has encouraged the scientific community to identify the precise role and molecular mechanisms of autophagy in aging, as targeting autophagy could be a novel therapy against aging and age‐related diseases.…”

Section: Impact Of Autophagy In Longevity and Agingmentioning

confidence: 97%

Autophagy in stem cell aging

2017

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SummaryAging is responsible for changes in mammalian tissues that result in an imbalance to tissue homeostasis and a decline in the regeneration capacity of organs due to stem cell exhaustion. Autophagy is a constitutive pathway necessary to degrade damaged organelles and protein aggregates. Autophagy is one of the hallmarks of aging, which involves a decline in the number and functionality of stem cells. Recent studies show that stem cells require autophagy to get rid of cellular waste produced during the quiescent stage. In particular, two independent studies in muscle and hematopoietic stem cells demonstrate the relevance of the autophagy impairment for stem cell exhaustion and aging. In this review, we summarize the main results of these works, which helped to elucidate the impact of autophagy in stem cell activity as well as in age‐associated diseases.

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Spermidine boosts autophagy to protect from synapse aging

Cited by 52 publications

References 0 publications

Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

eIF 5A is required for autophagy by mediating ATG 3 translation

Autophagy in stem cell aging

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