Caloric restriction induced epigenetic effects on aging

Aging is the subject of many studies, facilitating the discovery of many interventions. Epigenetic influences numerous life processes by regulating gene expression and also plays a crucial role in aging regulation. Increasing data suggests that dietary changes can alter epigenetic marks associated with aging. Caloric restriction (CR)is considered an intervention to regulate aging and prolong life span. At present, CR has made some progress by regulating signaling pathways associated with aging as well as the mechanism of action of intercellular signaling molecules against aging. In this review, we will focus on autophagy and epigenetic modifications to elaborate the molecular mechanisms by which CR delays aging by triggering autophagy, epigenetic modifications, and the interaction between the two in caloric restriction. In order to provide new ideas for the study of the mechanism of aging and delaying aging.

[1]  M. Wang,et al.  Sirt3 deficiency accelerates ovarian senescence without affecting spermatogenesis in aging mice. , 2022, Free radical biology & medicine.

[2]  H. Udono,et al.  Metformin-ROS-Nrf2 connection in the host defense mechanism against oxidative stress, apoptosis, cancers, and ageing. , 2022, Biochimica et biophysica acta. General subjects.

[3]  T. Pieber,et al.  The effect of spermidine on autoimmunity and beta cell function in NOD mice , 2022, Scientific Reports.

[4]  P. Bradshaw Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan , 2021, Antioxidants.

[5]  D. Ojcius,et al.  Recent advances in the field of caloric restriction mimetics and anti-aging molecules , 2020, Ageing Research Reviews.

[6]  Christine E. Heitsch,et al.  Mathematical and Computational Biology: A Combinatorial Approach to Single-Stranded Nucleotide Sequences , 2004 .

[7]  G. Kroemer,et al.  Triethylenetetramine (trientine): a caloric restriction mimetic with a new mode of action. , 2020, Autophagy.

[8]  L. Pulakat,et al.  Pro-Senescence and Anti-Senescence Mechanisms of Cardiovascular Aging: Cardiac MicroRNA Regulation of Longevity Drug-Induced Autophagy , 2020, Frontiers in Pharmacology.

[9]  P. Opolon,et al.  Chemical activation of SAT1 corrects diet-induced metabolic syndrome , 2020, Cell Death & Differentiation.

[10]  T. Saliev,et al.  Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research , 2020, Nutrients.

[11]  Yujue Wang,et al.  Research progress on sirtuins family members and cell senescence. , 2020, European journal of medicinal chemistry.

[12]  F. Boffo,et al.  Methylation of the Suppressor Gene p16INK4a: Mechanism and Consequences , 2020, Biomolecules.

[13]  X. Ji,et al.  Methionine Restriction and Cancer Biology , 2020, Nutrients.

[14]  C. Franceschi,et al.  Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver , 2020, Nutrients.

[15]  R. de Cabo,et al.  Effects of Intermittent Fasting on Health, Aging, and Disease. , 2019, The New England journal of medicine.

[16]  H. Chung,et al.  The Effects of Calorie Restriction on Autophagy: Role on Aging Intervention , 2019, Nutrients.

[17]  Blanca Olivia Murillo Ortiz,et al.  Recovery Of Bone And Muscle Mass In Patients With Chronic Kidney Disease And Iron Overload On Hemodialysis And Taking Combined Supplementation With Curcumin And Resveratrol , 2019, Clinical interventions in aging.

[18]  J. Bell,et al.  DNA Methylation Age and Physical and Cognitive Aging , 2019, The journals of gerontology. Series A, Biological sciences and medical sciences.

[19]  A. Ballabio,et al.  Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence , 2019, Molecular cell.

[20]  A. Hussain,et al.  Quercetin modifies 5′CpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells , 2019, Journal of cellular biochemistry.

[21]  Meng Wu,et al.  Metformin prevents murine ovarian aging , 2019, Aging.

[22]  George Bou-Gharios,et al.  Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300: response to correspondence by Borzì et al. , 2019, Experimental and Molecular Medicine.

[23]  O. Kepp,et al.  The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species , 2019, Nature Communications.

[24]  A. Trumpp,et al.  The long non-coding RNA Meg3 is dispensable for hematopoietic stem cells , 2019, Scientific Reports.

[25]  Yuhui Yang,et al.  Dietary methionine restriction reduces hepatic steatosis and oxidative stress in high-fat-fed mice by promoting H2S production. , 2019, Food & function.

[26]  S. Rizvi,et al.  Fisetin, a potential caloric restriction mimetic, attenuates senescence biomarkers in rat erythrocytes. , 2019, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[27]  P. Hegyi,et al.  Metformin induces significant reduction of body weight, total cholesterol and LDL levels in the elderly – A meta-analysis , 2018, PloS one.

[28]  R. de Cabo,et al.  A time to fast , 2018, Science.

[29]  V. Longo,et al.  Fasting and cancer: molecular mechanisms and clinical application , 2018, Nature Reviews Cancer.

[30]  Anuj Srivastava,et al.  A multi-tissue full lifespan epigenetic clock for mice , 2018, Aging.

[31]  Y. Anouar,et al.  AMPK Activation of PGC-1α/NRF-1-Dependent SELENOT Gene Transcription Promotes PACAP-Induced Neuroendocrine Cell Differentiation Through Tolerance to Oxidative Stress , 2018, Molecular Neurobiology.

[32]  Elsdon Storey,et al.  Effect of Aspirin on All‐Cause Mortality in the Healthy Elderly , 2018, The New England journal of medicine.

[33]  Suzanne G. Orchard,et al.  Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly , 2018, The New England journal of medicine.

[34]  Y. Nie,et al.  Fatty liver mediated by peroxisome proliferator‐activated receptor‐α DNA methylation can be reversed by a methylation inhibitor and curcumin , 2018, Journal of digestive diseases.

[35]  Hermann Stuppner,et al.  Higher spermidine intake is linked to lower mortality: a prospective population-based study. , 2018, The American journal of clinical nutrition.

[36]  L. Partridge,et al.  Short-Term, Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension , 2018, Current Biology.

[37]  Yan Li,et al.  SIRT3 deficiency exacerbates p53/Parkin‑mediated mitophagy inhibition and promotes mitochondrial dysfunction: Implication for aged hearts. , 2018, International journal of molecular medicine.

[38]  J. Tsien,et al.  Histone Deacetylase Inhibitor Alleviates the Neurodegenerative Phenotypes and Histone Dysregulation in Presenilins-Deficient Mice , 2018, Front. Aging Neurosci..

[39]  M. Latimer,et al.  Physiological and Molecular Mechanisms of Methionine Restriction , 2018, Front. Endocrinol..

[40]  K. Gulati,et al.  Recent studies on cellular and molecular mechanisms in Alzheimer’s disease: focus on epigenetic factors and histone deacetylase , 2018, Reviews in the neurosciences.

[41]  J. Speakman,et al.  The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon , 2018, Aging cell.

[42]  V. Gladyshev,et al.  Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction , 2018, Aging cell.

[43]  A. Zullo,et al.  Sirtuins as Mediator of the Anti-Ageing Effects of Calorie Restriction in Skeletal and Cardiac Muscle , 2018, International journal of molecular sciences.

[44]  W. Kraus,et al.  Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2‐isoprostanes: The CALERIE 2 randomized clinical trial , 2018, Aging cell.

[45]  J. Gil,et al.  Senescence and aging: Causes, consequences, and therapeutic avenues , 2018, The Journal of cell biology.

[46]  W. Freeman,et al.  Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation , 2018, Neurobiology of Aging.

[47]  J. Murabito,et al.  Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits , 2017, Aging cell.

[48]  D. Gillespie,et al.  AKT overactivation can suppress DNA repair via p70S6 kinase-dependent downregulation of MRE11 , 2017, Oncogene.

[49]  M. Alizadeh,et al.  Antioxidant properties of the flavonoid fisetin: An updated review of in vivo and in vitro studies , 2017 .

[50]  Jie Wei,et al.  Anthocyanins Delay Ageing-Related Degenerative Changes in the Liver , 2017, Plant Foods for Human Nutrition.

[51]  Jun Xie,et al.  Curcumin modulates covalent histone modification and TIMP1 gene activation to protect against vascular injury in a hypertension rat model , 2017, Experimental and therapeutic medicine.

[52]  Chaur-Jong Hu,et al.  Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus , 2017, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[53]  Tao Zhang,et al.  IGF‐1 promotes angiogenesis in endothelial cells/adipose‐derived stem cells co‐culture system with activation of PI3K/Akt signal pathway , 2017, Cell proliferation.

[54]  M. Holz,et al.  The therapeutic potential of resveratrol: a review of clinical trials , 2017, npj Precision Oncology.

[55]  L. Cui,et al.  Resveratrol suppresses melanoma by inhibiting NF-κB/miR-221 and inducing TFG expression , 2017, Archives of Dermatological Research.

[56]  R. Colman,et al.  Caloric restriction delays age-related methylation drift , 2017, Nature Communications.

[57]  P. Sassone-Corsi,et al.  Aged Stem Cells Reprogram Their Daily Rhythmic Functions to Adapt to Stress , 2017, Cell.

[58]  Mark S. Schmidt,et al.  Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging , 2017, Cell.

[59]  A. Matheu,et al.  Autophagy in stem cell aging , 2017, Aging cell.

[60]  E. Fukusaki,et al.  Epigenetic regulation of starvation-induced autophagy in Drosophila by histone methyltransferase G9a , 2017, Scientific Reports.

[61]  Caroline L. Wilson,et al.  Cellular senescence drives age-dependent hepatic steatosis , 2017, Nature Communications.

[62]  Lian-Hui Zhang,et al.  Phototrophy and starvation-based induction of autophagy upon removal of Gcn5-catalyzed acetylation of Atg7 in Magnaporthe oryzae , 2017, Autophagy.

[63]  B. Han,et al.  The effects of blueberry anthocyanins on histone acetylation in rat liver fibrosis. , 2017, Oncotarget.

[64]  N. Al-Dhabi,et al.  Methionine restriction on oxidative stress and immune response in dss-induced colitis mice , 2017, Oncotarget.

[65]  W. Freeman,et al.  Role of DNA methylation in the dietary restriction mediated cellular memory , 2017, GeroScience.

[66]  Sang-Goo Lee,et al.  Using DNA Methylation Profiling to Evaluate Biological Age and Longevity Interventions. , 2017, Cell metabolism.

[67]  Peter D. Adams,et al.  Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment , 2017, Genome Biology.

[68]  O. Hendrich,et al.  Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism , 2017, Genome Biology.

[69]  M. Dozmorov,et al.  Age-associated DNA methylation changes in naive CD4+ T cells suggest an evolving autoimmune epigenotype in aging T cells. , 2017, Epigenomics.

[70]  David M. Sabatini,et al.  mTOR Signaling in Growth, Metabolism, and Disease , 2017, Cell.

[71]  Hang Zhang,et al.  The effects of methionine on TCE-induced DNA methylation and mRNA expression changes in mouse liver , 2017, Molecular & Cellular Toxicology.

[72]  J. Locasale,et al.  Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice , 2017, Experimental Gerontology.

[73]  Traci L. Marin,et al.  AMPK promotes mitochondrial biogenesis and function by phosphorylating the epigenetic factors DNMT1, RBBP7, and HAT1 , 2017, Science Signaling.

[74]  B. Fu,et al.  Alleviation of senescence and epithelial-mesenchymal transition in aging kidney by short-term caloric restriction and caloric restriction mimetics via modulation of AMPK/mTOR signaling , 2017, Oncotarget.

[75]  D. Wanders,et al.  FGF21 Mediates the Thermogenic and Insulin-Sensitizing Effects of Dietary Methionine Restriction but Not Its Effects on Hepatic Lipid Metabolism , 2017, Diabetes.

[76]  D. Allison,et al.  Caloric restriction improves health and survival of rhesus monkeys , 2017, Nature Communications.

[77]  M. Horowitz,et al.  Methionine‐Restricted Diet Increases miRNAs That Can Target RUNX2 Expression and Alters Bone Structure in Young Mice , 2017, Journal of cellular biochemistry.

[78]  Tony Wyss-Coray,et al.  Ageing, neurodegeneration and brain rejuvenation , 2016, Nature.

[79]  A. Kirmizis,et al.  Loss of Nat4 and its associated histone H4 N‐terminal acetylation mediates calorie restriction‐induced longevity , 2016, EMBO reports.

[80]  Xin Zheng,et al.  P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma by promoting cell autophagy , 2016, Cell Death and Disease.

[81]  Byoung-Chul Kim,et al.  Short‐term calorie restriction ameliorates genomewide, age‐related alterations in DNA methylation , 2016, Aging cell.

[82]  S. H. Baek,et al.  Epigenetic and transcriptional regulation of autophagy , 2016, Autophagy.

[83]  G. Jena,et al.  Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. , 2016, Chemico-biological interactions.

[84]  J. Tyler,et al.  Epigenetics and aging , 2016, Science Advances.

[85]  S. Kritchevsky,et al.  Metformin as a Tool to Target Aging. , 2016, Cell metabolism.

[86]  A. Pegg Functions of Polyamines in Mammals* , 2016, The Journal of Biological Chemistry.

[87]  R. Sinha,et al.  Methionine-restricted diet inhibits growth of MCF10AT1-derived mammary tumors by increasing cell cycle inhibitors in athymic nude mice , 2016, BMC Cancer.

[88]  Dudley Lamming,et al.  Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer , 2016, Aging cell.

[89]  L. Guarente,et al.  Caloric restriction blocks neuropathology and motor deficits in Machado–Joseph disease mouse models through SIRT1 pathway , 2016, Nature Communications.

[90]  D. Lombard,et al.  Finding Ponce de Leon’s Pill: Challenges in Screening for Anti-Aging Molecules , 2016, F1000Research.

[91]  Hening Lin,et al.  A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity. , 2016, Cancer cell.

[92]  Zhongchi Li,et al.  Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling , 2016, Cell cycle.

[93]  C. Marsh,et al.  Aging is associated with hypermethylation of autophagy genes in macrophages , 2016, Epigenetics.

[94]  N. Veronese,et al.  Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle. , 2016, Cell reports.

[95]  U. Sauer,et al.  Life span extension by targeting a link between metabolism and histone acetylation in Drosophila , 2016, EMBO reports.

[96]  G. López-Lluch,et al.  Calorie restriction as an intervention in ageing , 2016, The Journal of physiology.

[97]  P. Giannakakou,et al.  A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity. , 2016, Cancer cell.

[98]  C. Chai,et al.  Roles of oxidative stress and the ERK1/2, PTEN and p70S6K signaling pathways in arsenite-induced autophagy. , 2015, Toxicology letters.

[99]  Yongjian Wu,et al.  Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway , 2015, PloS one.

[100]  Robi Tacutu,et al.  Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging , 2015, Genome Biology.

[101]  J. Locasale,et al.  Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism. , 2015, Cell metabolism.

[102]  H. Steinbusch,et al.  Epigenetic modifications in mouse cerebellar Purkinje cells: effects of aging, caloric restriction, and overexpression of superoxide dismutase 1 on 5-methylcytosine and 5-hydroxymethylcytosine , 2015, Neurobiology of Aging.

[103]  Kun-Ling Tsai,et al.  Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. , 2015, Molecular nutrition & food research.

[104]  R. Sharma,et al.  Age- and Tissue-Dependent Modulation of IGF-1/PI3K/Akt Protein Expression by Dietary Restriction in Mice , 2015, Hormone and Metabolic Research.

[105]  K. Kwon,et al.  Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast , 2015, eLife.

[106]  P. Nelson,et al.  MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation , 2015, Nature Cell Biology.

[107]  F. Wang,et al.  β‐Guanidinopropionic acid extends the lifespan of Drosophila melanogaster via an AMP‐activated protein kinase‐dependent increase in autophagy , 2015, Aging cell.

[108]  K. S. Bhullar,et al.  Lifespan and healthspan extension by resveratrol. , 2015, Biochimica et biophysica acta.

[109]  Z. Ling,et al.  SIRT3‐dependent GOT2 acetylation status affects the malate–aspartate NADH shuttle activity and pancreatic tumor growth , 2015, The EMBO journal.

[110]  L. Partridge,et al.  Promoting Health and Longevity through Diet: From Model Organisms to Humans , 2015, Cell.

[111]  G. Rimbach,et al.  Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity. , 2015, Rejuvenation research.

[112]  Min Jung Park,et al.  Abstract T MP20: Histone Methylation Patterns in Astrocytes are Influenced by Age Following Ischemia , 2015, Stroke.

[113]  J. Praestgaard,et al.  mTOR inhibition improves immune function in the elderly , 2014, Science Translational Medicine.

[114]  M. Filip,et al.  A Comprehensive View of the Epigenetic Landscape. Part II: Histone Post-translational Modification, Nucleosome Level, and Chromatin Regulation by ncRNAs , 2014, Neurotoxicity Research.

[115]  Weiwei Dang,et al.  Histone methylation and aging: lessons learned from model systems. , 2014, Biochimica et biophysica acta.

[116]  R. Sinha,et al.  Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice , 2014, The Prostate.

[117]  J. Halcox,et al.  Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non‐diabetic controls , 2014, Diabetes, obesity & metabolism.

[118]  C. Leeuwenburgh,et al.  Calorie restriction combined with resveratrol induces autophagy and protects 26-month-old rat hearts from doxorubicin-induced toxicity. , 2014, Free radical biology & medicine.

[119]  S. Safe,et al.  Mechanism of Metformin-dependent Inhibition of Mammalian Target of Rapamycin (mTOR) and Ras Activity in Pancreatic Cancer , 2014, The Journal of Biological Chemistry.

[120]  M. Röösli,et al.  Modulation of Age- and Cancer-Associated DNA Methylation Change in the Healthy Colon by Aspirin and Lifestyle , 2014, Journal of the National Cancer Institute.

[121]  C. Wyse,et al.  Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21 , 2014, Aging cell.

[122]  Michael J. MacDonald,et al.  Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase , 2014, Nature.

[123]  G. Kroemer,et al.  Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification , 2014, PLoS genetics.

[124]  V. Gladyshev,et al.  Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino acid status , 2014, Nature Communications.

[125]  Yu-Ting Wu,et al.  Role of AMPK-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress. , 2014, Biochimica et biophysica acta.

[126]  C. López-Otín,et al.  Regulation of autophagy by cytosolic acetyl-coenzyme A. , 2014, Molecular cell.

[127]  Sang Gyun Kim,et al.  Rapamycin: one drug, many effects. , 2014, Cell metabolism.

[128]  B. Tu,et al.  Methionine is a signal of amino acid sufficiency that inhibits autophagy through the methylation of PP2A , 2014, Autophagy.

[129]  Yawei Xu,et al.  Enhancement in efferocytosis of oxidized low-density lipoprotein-induced apoptotic RAW264.7 cells through Sirt1-mediated autophagy , 2013, International journal of molecular medicine.

[130]  Sujoy Ghosh,et al.  Transcriptional impact of dietary methionine restriction on systemic inflammation: Relevance to biomarkers of metabolic disease during aging , 2014, BioFactors.

[131]  Keiji Tanaka,et al.  Proteostasis and neurodegeneration: the roles of proteasomal degradation and autophagy. , 2014, Biochimica et biophysica acta.

[132]  S. Mazzuco,et al.  Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study “Treviso Longeva (TRELONG)” , 2014, AGE.

[133]  P. Hof,et al.  Histone deacetylase 2 in the mouse hippocampus: attenuation of age-related increase by caloric restriction. , 2013, Current Alzheimer research.

[134]  Supriyo De,et al.  Age-related changes in microRNA levels in serum , 2013, Aging.

[135]  E. Mercken,et al.  Age-associated miRNA Alterations in Skeletal Muscle from Rhesus Monkeys reversed by caloric restriction , 2013, Aging.

[136]  L. Zitvogel,et al.  Autophagy and cellular immune responses. , 2013, Immunity.

[137]  O. Hermanson,et al.  The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy , 2013, Nature.

[138]  B. Tu,et al.  Methionine Inhibits Autophagy and Promotes Growth by Inducing the SAM-Responsive Methylation of PP2A , 2013, Cell.

[139]  Juan Chen,et al.  SIRT2 overexpression in hepatocellular carcinoma mediates epithelial to mesenchymal transition by protein kinase B/glycogen synthase kinase‐3β/β‐catenin signaling , 2013, Hepatology.

[140]  Qin-Li Wan,et al.  Aspirin extends the lifespan of Caenorhabditis elegans via AMPK and DAF-16/FOXO in dietary restriction pathway , 2013, Experimental Gerontology.

[141]  Xiaoling Xu,et al.  SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. , 2013, Cancer cell.

[142]  David Weinkove,et al.  Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism , 2013, Cell.

[143]  J. Tischfield,et al.  The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation. , 2013, Genes & development.

[144]  R. Cardiff,et al.  ATG proteins mediate efferocytosis and suppress inflammation in mammary involution , 2013, Autophagy.

[145]  David I. K. Martin,et al.  Deep sequencing identifies circulating mouse miRNAs that are functionally implicated in manifestations of aging and responsive to calorie restriction , 2013, Aging.

[146]  J. Mehta,et al.  Aspirin inhibits oxidant stress, reduces age-associated functional declines, and extends lifespan of Caenorhabditis elegans. , 2013, Antioxidants & redox signaling.

[147]  K. Fritz Chemical acetylation and deacetylation. , 2013, Methods in molecular biology.

[148]  J. Mitchell,et al.  Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR. , 2013, The Biochemical journal.

[149]  N. Orentreich,et al.  Methionine-Restricted C57BL/6J Mice Are Resistant to Diet-Induced Obesity and Insulin Resistance but Have Low Bone Density , 2012, PloS one.

[150]  A. Regev,et al.  The Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolism , 2012, Cell.

[151]  M. Fenech,et al.  A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. , 2012, Cancer treatment reviews.

[152]  F. Slack,et al.  Novel MicroRNAs Differentially Expressed during Aging in the Mouse Brain , 2012, PloS one.

[153]  P. Hof,et al.  Age-related increase in levels of 5-hydroxymethylcytosine in mouse hippocampus is prevented by caloric restriction. , 2012, Current Alzheimer research.

[154]  C. Deng,et al.  SIRT3 is a mitochondrial tumor suppressor: a scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis. , 2012, Cancer research.

[155]  R. Pamplona,et al.  Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria , 2012, Biogerontology.

[156]  Li Yu,et al.  Function and Molecular Mechanism of Acetylation in Autophagy Regulation , 2012, Science.

[157]  D. Hardie,et al.  AMPK: a nutrient and energy sensor that maintains energy homeostasis , 2012, Nature Reviews Molecular Cell Biology.

[158]  Dudley Lamming,et al.  Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity , 2012, Science.

[159]  J. Son,et al.  Neuronal autophagy and neurodegenerative diseases , 2012, Experimental & Molecular Medicine.

[160]  V. Anisimov,et al.  Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice , 2011, Cell cycle.

[161]  R. Schneider,et al.  Targeting the mTOR/4E-BP Pathway in Endometrial Cancer , 2011, Clinical Cancer Research.

[162]  A. Krogh,et al.  microRNA‐101 is a potent inhibitor of autophagy , 2011, The EMBO journal.

[163]  X. Wang,et al.  SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. , 2011, Cancer cell.

[164]  D. Green,et al.  Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging , 2011, Science.

[165]  Enxuan Jing,et al.  Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production , 2011, Proceedings of the National Academy of Sciences.

[166]  Zheng Yan,et al.  Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. , 2011, Cell metabolism.

[167]  E. Verdin,et al.  SIRT3 and cancer: tumor promoter or suppressor? , 2011, Biochimica et biophysica acta.

[168]  H. Steinbusch,et al.  Caloric restriction attenuates age-related changes of DNA methyltransferase 3a in mouse hippocampus , 2011, Brain, Behavior, and Immunity.

[169]  Harshini Sarojini,et al.  Gain of survival signaling by down-regulation of three key miRNAs in brain of calorie-restricted mice , 2011, Aging.

[170]  T. Tollefsbol,et al.  p16INK4a Suppression by Glucose Restriction Contributes to Human Cellular Lifespan Extension through SIRT1-Mediated Epigenetic and Genetic Mechanisms , 2011, PloS one.

[171]  P. Bénit,et al.  Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome , 2011, The Journal of cell biology.

[172]  D. Underhill,et al.  Comparative Analyses of SUV420H1 Isoforms and SUV420H2 Reveal Differences in Their Cellular Localization and Effects on Myogenic Differentiation , 2010, PloS one.

[173]  Wei Yu,et al.  Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction , 2010, Cell.

[174]  Xiaoling Xu,et al.  Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. , 2010, Cell metabolism.

[175]  A. Cuervo,et al.  Altered lipid content inhibits autophagic vesicular fusion , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[176]  Hui Zhang,et al.  Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity , 2010, Nature Cell Biology.

[177]  A. Donker,et al.  Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial , 2010, BMJ : British Medical Journal.

[178]  M. Fujita,et al.  Novel heart failure therapy targeting transcriptional pathway in cardiomyocytes by a natural compound, curcumin. , 2010, Circulation journal : official journal of the Japanese Circulation Society.

[179]  Chang Hwa Jung,et al.  mTOR regulation of autophagy , 2010, FEBS letters.

[180]  Nektarios Tavernarakis,et al.  Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol , 2009, Aging.

[181]  Frank Sinner,et al.  Induction of autophagy by spermidine promotes longevity , 2009, Nature Cell Biology.

[182]  Gene Kim,et al.  Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. , 2009, The Journal of clinical investigation.

[183]  Xiuping Liu,et al.  Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells , 2009, Autophagy.

[184]  Sterling C. Johnson,et al.  Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys , 2009, Science.

[185]  P. Puigserver,et al.  AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity , 2009, Nature.

[186]  Qing Xu,et al.  Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. , 2009, Cell metabolism.

[187]  E. Nishida,et al.  Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans , 2009, Nature.

[188]  R. Levine,et al.  Methionine in proteins defends against oxidative stress , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[189]  Jason K. Kim,et al.  Fibroblast Growth Factor 21 Reverses Hepatic Steatosis, Increases Energy Expenditure, and Improves Insulin Sensitivity in Diet-Induced Obese Mice , 2009, Diabetes.

[190]  S. Varambally,et al.  Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in Cancer , 2008, Science.

[191]  Jianping Ye,et al.  Inhibition of transcriptional activity of c-JUN by SIRT1. , 2008, Biochemical and biophysical research communications.

[192]  N. Ruderman,et al.  SIRT1 Modulation of the Acetylation Status, Cytosolic Localization, and Activity of LKB1 , 2008, Journal of Biological Chemistry.

[193]  R. Klein,et al.  Brain IGF-1 Receptors Control Mammalian Growth and Lifespan through a Neuroendocrine Mechanism , 2008, PLoS biology.

[194]  O. Maes,et al.  Murine microRNAs implicated in liver functions and aging process , 2008, Mechanisms of Ageing and Development.

[195]  Andrzej Bartke,et al.  Impact of reduced insulin‐like growth factor‐1/insulin signaling on aging in mammals: novel findings , 2008, Aging cell.

[196]  M. Fukuoka,et al.  Curcumin prevents and reverses murine cardiac hypertrophy. , 2008, The Journal of clinical investigation.

[197]  A. Brech,et al.  Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila , 2008, Autophagy.

[198]  A. Camara,et al.  Inhibited mitochondrial respiration by amobarbital during cardiac ischaemia improves redox state and reduces matrix Ca2+ overload and ROS release. , 2007, Cardiovascular research.

[199]  Q. Tong,et al.  SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction , 2007, Aging cell.

[200]  Lewis C. Cantley,et al.  AKT/PKB Signaling: Navigating Downstream , 2007, Cell.

[201]  Yue-zhong Wu,et al.  Diverse histone modifications on histone 3 lysine 9 and their relation to DNA methylation in specifying gene silencing , 2007, BMC Genomics.

[202]  Jiri Bartek,et al.  p16INK4A is a robust in vivo biomarker of cellular aging in human skin , 2006, Aging cell.

[203]  M. Rigoulet,et al.  The ROS Production Induced by a Reverse-Electron Flux at Respiratory-Chain Complex 1 is Hampered by Metformin , 2006, Journal of bioenergetics and biomembranes.

[204]  T. Bestor,et al.  Eukaryotic cytosine methyltransferases. , 2005, Annual review of biochemistry.

[205]  R. Anson,et al.  The diet restriction paradigm: a brief review of the effects of every-other-day feeding , 2005, AGE.

[206]  M. Smith-Wheelock,et al.  Methionine‐deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF‐I and insulin levels, and increases hepatocyte MIF levels and stress resistance , 2005, Aging cell.

[207]  S. Nemoto,et al.  Nutrient Availability Regulates SIRT1 Through a Forkhead-Dependent Pathway , 2004, Science.

[208]  K. McManus,et al.  Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development. , 2004, Developmental biology.

[209]  J. Wood,et al.  Sirtuin activators mimic caloric restriction and delay ageing in metazoans , 2004, Nature.

[210]  Myriam Gorospe,et al.  Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase , 2004, Science.

[211]  S. Benzer,et al.  Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway , 2004, Current Biology.

[212]  Steven P. Gygi,et al.  Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase , 2004, Science.

[213]  P. Defossez,et al.  Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. , 2000, Science.

[214]  P. Marks,et al.  Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[215]  D. Haber,et al.  DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development , 1999, Cell.

[216]  M. Greenberg,et al.  Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor , 1999, Cell.

[217]  A. Matsuura,et al.  Acidification of vacuoles is required for autophagic degradation in the yeast, Saccharomyces cerevisiae. , 1997, Journal of biochemistry.

[218]  E. Stadtman,et al.  Methionine residues as endogenous antioxidants in proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[219]  J. A. Zimmerman,et al.  Methionine restriction increases blood glutathione and longevity in F344 rats , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[220]  C. Kenyon,et al.  A C. elegans mutant that lives twice as long as wild type , 1993, Nature.

[221]  T. Sugimura,et al.  Quantitative nutritional studies with water-soluble, chemically defined diets. VIII. The forced feeding of diets each lacking in one essential amino acid. , 1959, Archives of biochemistry and biophysics.

[222]  J. Greenstein,et al.  Quantitative nutritional studies with water-soluble, chemically defined diets. III. Individual amino acids as sources of non-essential nitrogen. , 1957, Archives of biochemistry and biophysics.