The Effects of Calorie Restriction on Autophagy: Role on Aging Intervention

Chung, Ki Wung; Chung, Hae Young

doi:10.3390/nu11122923

Cited by 61 publications

(32 citation statements)

References 133 publications

(156 reference statements)

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“…50 Therefore, treatments that enhance the breakdown of ferritin, which is dependent on autophagy, [51][52][53] may be beneficial. As autophagy is clearly disrupted in old muscles, 54 we propose that interventions that stimulate autophagy such as rapamycin treatment 55 and calorie restriction 56 could improve skeletal muscle iron homeostasis via facilitating ferritinophagy.…”

Section: Oral Administration Of An Iron Chelator (Deferiprone) Does Nmentioning

confidence: 99%

Iron accumulation in skeletal muscles of old mice is associated with impaired regeneration after ischaemia–reperfusion damage

Alves

Kysenius

Caldow

et al. 2021

J cachexia sarcopenia muscle

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Background Oxidative stress is implicated in the insidious loss of muscle mass and strength that occurs with age. However, few studies have investigated the role of iron, which is elevated during ageing, in age-related muscle wasting and blunted repair after injury. We hypothesized that iron accumulation leads to membrane lipid peroxidation, muscle wasting, increased susceptibility to injury, and impaired muscle regeneration. Methods To examine the role of iron in age-related muscle atrophy, we compared the skeletal muscles of 3-month-old with 22-to 24-month-old 129SvEv FVBM mice. We assessed iron distribution and total elemental iron using laser ablation inductively coupled plasma mass spectrometry and Perls' stain on skeletal muscle cross-sections. In addition, old mice underwent ischaemia-reperfusion (IR) injury (90 min ischaemia), and muscle regeneration was assessed 14 days after injury. Immunoblotting was used to determine lipid peroxidation (4HNE) and iron-related proteins. To determine whether muscle iron content can be altered, old mice were treated with deferiprone (DFP) in the drinking water, and we assessed its effects on muscle regeneration after injury. Results We observed a significant increase in total elemental iron (+43%, P < 0.05) and lipid peroxidation (4HNE: +76%, P < 0.05) in tibialis anterior muscles of old mice. Iron was further increased after injury (adult: +81%, old: +135%, P < 0.05) and associated with increased lipid peroxidation (+41%, P < 0.05). Administration of DFP did not impact iron or measures of lipid peroxidation in skeletal muscle or modulate muscle mass. Increased muscle iron concentration and lipid peroxidation were associated with less efficient regeneration, evident from the smaller fibres in cross-sections of tibialis anterior muscles (À24%, P < 0.05) and an increased percentage of fibres with centralized nuclei (+4124%, P < 0.05) in muscles of old compared with adult mice. Administration of DFP lowered iron after IR injury (PRE: À32%, P < 0.05 and POST: À41%, P < 0.05), but did not translate to structural improvements. Conclusions Muscles from old mice have increased iron levels, which are associated with increased lipid peroxidation, increased susceptibility to IR injury, and impaired muscle regeneration. Our results suggest that iron is involved in effective muscle regeneration, highlighting the importance of iron homeostasis in muscle atrophy and muscle repair.

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Section: Oral Administration Of An Iron Chelator (Deferiprone) Does Nmentioning

confidence: 99%

Iron accumulation in skeletal muscles of old mice is associated with impaired regeneration after ischaemia–reperfusion damage

Alves

Kysenius

Caldow

et al. 2021

J cachexia sarcopenia muscle

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“…Aging decreases the autophagosome–lysosome fusion, which causes a defect in downstream autophagic signal transduction 14 . In contrast, caloric restriction (CR) induces autophagy, stimulates the autophagosome formation and delays aging 15,16 . The mechanisms that regulate autophagosome formation signaling were identified through studies of CR, although little information is available about autophagosome–lysosome fusion signaling.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics analysis of autophagy‐lysosomal degradation in cardiac aging

Kamihara

Murohara

2020

Geriatrics Gerontology Int

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AimCardiac aging, which causes cardiac diastolic dysfunction, frequently occurs in older people. The role of autophagy in cardiac aging is the subject of intensive research. Autophagy comprises steps called the autophagosome formation and autophagosome–lysosome fusion. Caloric restriction (CR) is the gold standard used to induce autophagosome formation, and autophagosome–lysosome fusion is reduced by aging. However, few studies are available that survey and compare signaling during CR (autophagosome formation induced status) and old (potentially autophagosome–lysosome fusion‐reduced status). Here we aimed to identify the rate‐limiting step of autophagic disorders during cardiac aging.MethodsWe employed bioinformatics to analyze publicly available DNA microarray datasets. The first dataset compared the hearts of young and old C57BL6 mice (OLD). The second dataset compared the hearts of young C57BL6 mice fed a normal diet with those of young C57BL6 mice subjected to CR.ResultsWe analyzed OLD‐upregulated genes that were significantly associated with the Gene Ontogeny term “Autophagy,” indicating that autophagic genes were upregulated in OLD mice. The autophagy‐related gene Atg5 and Atg5‐related genes were upregulated in OLD and CR mice. The identified hub and bottleneck genes are autophagic autophagosome formation suppressors such as Sirt2, Ilk and Islr, as well as the autophagosome–lysosome fusion inducer Snapin.ConclusionsAutophagosome formation genes were upregulated in aging mice subjected to CR, indicating that an upregulated autophagosome formation is not a change specific to cardiac aging. However, autophagosome–lysosome fusion genes, particularly the lysosome transportation‐related gene Snapin, were downregulated in aging, indicating that autophagosome–lysosome fusion may cause autophagic disorders in cardiac aging. Geriatr Gerontol Int 2021; 21: 108–115.

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“…Meanwhile, insufficient of autophagy will cause carcinogenesis by accumulating several carcinogenic factors [11,12] ; Hypoxia or starvation can induce autophagy to scavenge the free radicals in cells for avoiding cell damage or to recycle nutrients to maintain cell survival [13][14][15] ; Furthermore, autophagy has also been found to cause chemotherapy resistance [16][17][18][19][20] . Apoptosis, an actively occurring programmed cell death under the control of apoptotic genes, was first proposed in 1972 by Kerr et al [21] .…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of MicroRNA-155 Regulated Autophagy and Apoptosis by targeting gene Rictor/Fos in Gastric Cancer Progression

Chen

Ren

et al. 2020

Preprint

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BACKGROUND Microrna-155 plays an important role in the pathogenesis, progression and treatment of various cancers. It is abnormally expressed in gastric cancer, but its expression level, mechanism and significance are controversial in different studies. So we make the study to explore the expression level, significance and mechanism of microRNA-155 on gastric cancer. METHODS Target genes of microRNA-155 in TargetScan and mirDB databases were analyzed by Wayne Mapping, Enrichr database, String database, TIMER database. Forty-three pairs of cancer tissues and adjacent tissues were collected to extract total RNA and protein. Expression of MicroRNA-155, Rictor, Fos, Beclin1, LC3, caspase3 and caspase9 were measured by qRT-PCR and western blot. The relationship between gene expression and clinicopathological factors were analyzed. SPSS 23.0 was used for statistical analysis. RESULTS A total of 700 (miRDB) and 556 (TargetScan) target genes were obtained and 280 genes were in the intersection of Wayne Mapping, 49 of them had a target score of 90 or more. GO and KEGG analysis revealed that they were related to autophagy or apoptosis pathway. Rictor and Fos were selected as research objects. Thirty-two cases showed high microRNA-155 expression (group H) and 11 cases showed low expression (group L). Twelve patients had high Rictor expression and 31 patients had low expression; Thirteen cases had roughly normal Fos expression and 30 cases had low or negative expression; Thirty-three cases had high Beclin1/LC3 expression and 10 cases had low expression; Ten cases had high caspase3/caspase9 expression and 33 cases had low expression. According to the results of immunohistochemistry and western blot, Rictor, Fos, caspase3 and caspase9 were low expressed while Beclin1 and LC3 were high expressed in group H. However, all the six genes had no significant difference in group L. CONCLUSIONS The abnormal expression of microRNA-155 may indicate the occurrence of gastric cancer and its expression level is negatively correlated with clinical stage of cancer. The down-regulated expression of Rictor and Fos, enhancement of autophagy and weakening of apoptosis may be related to the over-expression of microRNA-155. MicroRNA-155 may promote the progression of gastric cancer by promoting autophagy and inhibiting apoptosis.

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The Effects of Calorie Restriction on Autophagy: Role on Aging Intervention

Cited by 61 publications

References 133 publications

Iron accumulation in skeletal muscles of old mice is associated with impaired regeneration after ischaemia–reperfusion damage

Iron accumulation in skeletal muscles of old mice is associated with impaired regeneration after ischaemia–reperfusion damage

Bioinformatics analysis of autophagy‐lysosomal degradation in cardiac aging

Clinical Significance of MicroRNA-155 Regulated Autophagy and Apoptosis by targeting gene Rictor/Fos in Gastric Cancer Progression

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