Abstract
Human longevity is a complex trait in which genetics, epigenetics, environmental and stochasticity differently contribute. To disentangle the complexity, our studies on genetics of longevity were, at the beginning, mainly focused on the extreme phenotypes, i.e. centenarians who escaped the major age-related diseases compared with cross sectional cohorts. Recently, we implemented this model by studying centenarians’ offspring and offspring of non-long lived parents. In association, during studies on many candidate genes SNPs, positively or negatively correlated with longevity have been identified. The results obtained on Insulin-like Growth Factor 1 Receptor (IGF1R) polymorphisms showed a correlation between specific genetic variants combinations and the low plasma level of IGF1 in centenarians, suggesting an impact of the IGF-I/insulin pathway on human longevity. This pathway together with mammalian target of rapamycin (mTOR) will be reviewed as being the most promising for longevity. Further, we will summarise the role of apolipoprotein E (APOE) variants in human longevity since the results of the large European project GEHA (Genetics of Healthy Aging) indicate APOE among the chromosomal loci associated with longevity. On the other hand, the identification of longevity-related genes does not explain the mechanisms of healthy aging and longevity rather pose questions on epigenetic contribution, gene regulation and the interactions with essential genomes, i.e. mitochondrial DNA and microbiota. To fully disentangle what appears to be an endless quest, all the components of the complexity of human longevity genetics are taken into account.
Keywords: Longevity, epigenetics, IGF-1, mTOR, APOE, ELOVL2, mtDNA, microbiota.
Current Vascular Pharmacology
Title:Genes of Human Longevity: An Endless Quest?
Volume: 12 Issue: 5
Author(s): Miriam Capri, Aurelia Santoro, Paolo Garagnani, Maria Giulia Bacalini, Chiara Pirazzini, Fabiola Olivieri, Antonio Procopio, Stefano Salvioli and Claudio Franceschi
Affiliation:
Keywords: Longevity, epigenetics, IGF-1, mTOR, APOE, ELOVL2, mtDNA, microbiota.
Abstract: Human longevity is a complex trait in which genetics, epigenetics, environmental and stochasticity differently contribute. To disentangle the complexity, our studies on genetics of longevity were, at the beginning, mainly focused on the extreme phenotypes, i.e. centenarians who escaped the major age-related diseases compared with cross sectional cohorts. Recently, we implemented this model by studying centenarians’ offspring and offspring of non-long lived parents. In association, during studies on many candidate genes SNPs, positively or negatively correlated with longevity have been identified. The results obtained on Insulin-like Growth Factor 1 Receptor (IGF1R) polymorphisms showed a correlation between specific genetic variants combinations and the low plasma level of IGF1 in centenarians, suggesting an impact of the IGF-I/insulin pathway on human longevity. This pathway together with mammalian target of rapamycin (mTOR) will be reviewed as being the most promising for longevity. Further, we will summarise the role of apolipoprotein E (APOE) variants in human longevity since the results of the large European project GEHA (Genetics of Healthy Aging) indicate APOE among the chromosomal loci associated with longevity. On the other hand, the identification of longevity-related genes does not explain the mechanisms of healthy aging and longevity rather pose questions on epigenetic contribution, gene regulation and the interactions with essential genomes, i.e. mitochondrial DNA and microbiota. To fully disentangle what appears to be an endless quest, all the components of the complexity of human longevity genetics are taken into account.
Export Options
About this article
Cite this article as:
Capri Miriam, Santoro Aurelia, Garagnani Paolo, Bacalini Giulia Maria, Pirazzini Chiara, Olivieri Fabiola, Procopio Antonio, Salvioli Stefano and Franceschi Claudio, Genes of Human Longevity: An Endless Quest?, Current Vascular Pharmacology 2014; 12 (5) . https://dx.doi.org/10.2174/1570161111666131219110301
DOI https://dx.doi.org/10.2174/1570161111666131219110301 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
Advancements in Arterial Stiffness: Novel Therapeutic Frontiers
Arterial stiffness, a hallmark of cardiovascular disease, poses significant challenges in contemporary healthcare. This thematic issue delves into the multifaceted landscape of arterial stiffness and explores cutting-edge therapeutic interventions aimed at mitigating its adverse effects. Within these pages, readers will find a comprehensive overview of the mechanisms underlying arterial stiffness, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Tetracyclines: Drugs with Huge Therapeutic Potential
Mini-Reviews in Medicinal Chemistry Lambert-Eaton Myasthenic Syndrome: A Very Rare and Tortuously Exasperating Facet of Pre-Synaptic Disorder of Neuromuscular Junction
Current Immunology Reviews (Discontinued) PET Imaging of the Peripheral Benzodiazepine Receptor: Monitoring Disease Progression and Therapy Response in Neurodegenerative Disorders
Current Pharmaceutical Design Study of Irisin Hormone Level in Type 2 Diabetic Patients and Patients with Diabetic Nephropathy
Current Diabetes Reviews Diabetes-induced Epigenetic Signature in Vascular Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets A Clinical Review on Nutritional Requirements and Assessment for Type 2 Diabetes Mellitus with Chronic Renal Disease
Current Diabetes Reviews Diabetes Mellitus and Vascular Endothelial Dysfunction: Current Perspectives
Current Vascular Pharmacology Serum Insulin Degrading Enzyme Level and Other Factors in Type 2 Diabetic Patients with Mild Cognitive Impairment
Current Alzheimer Research Micro Arrays and Biochips: Applications and Potential in Genomics and Proteomics
Current Genomics Aldose Reductase Inhibitors from the Nature
Current Medicinal Chemistry Coumarins as Promising Scaffold for the Treatment of Age-related Diseases – An Overview of the Last Five Years
Current Topics in Medicinal Chemistry Inhibitors of Cyclin-Dependent Kinases: Potential Drugs for the Treatment of Neurodegenerative Disorders?
Current Medicinal Chemistry - Central Nervous System Agents AZT: An Old Drug with New Perspectives
Current Clinical Pharmacology Dynamic Expression of MicroRNAs (183, 135a, 125b, 128, 30c and 27a) in the Rat Pilocarpine Model and Temporal Lobe Epilepsy Patients
CNS & Neurological Disorders - Drug Targets Bile Acids and Farnesoid X Receptor: Novel Target for the Treatment of Diabetic Cardiomyopathy
Current Protein & Peptide Science Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes
Current Diabetes Reviews Imaging of Organ Metabolism in Obesity and Diabetes: Treatment Perspectives
Current Pharmaceutical Design The Role of Calcium Stores in Apoptosis and Autophagy
Current Molecular Medicine Biochemical Strategies to Anticoagulation: A Comparative Overview
Current Vascular Pharmacology Chondroitin Sulfate, a Major Niche Substance of Neural Stem Cells, and Cell Transplantation Therapy of Neurodegeneration Combined with Niche Modification
Current Stem Cell Research & Therapy