Free radical hypothesis of aging emphasized that the age-related accumulation of free radicals results in cell injury. Alzheimer's disease (AD) is the most common form of neurodegenerative disease characterized by impaired cognition and memory of the elderly. Aging is a key risk factor in AD. Substantial evidence suggests that imbalance between free radical formation and clearance promotes AD pathogenesis. The brain overcomes oxidative stress by inducing expression of a set of genes called vitagenes. The protein products of vitagenes include heat shock proteins, heme oxygenases and thioredoxin systems, which serve as endogenous lifeguard of cells. This paper is a review of the expression and function of vitagenes in aging and AD brain, as well as relevant pharmacological study.
Aging ; genetics ; metabolism ; Alzheimer Disease ; genetics ; metabolism ; Brain ; metabolism ; Heat-Shock Proteins ; genetics ; metabolism ; Heme Oxygenase (Decyclizing) ; genetics ; metabolism ; Humans ; Oxidative Stress ; Thioredoxins ; genetics ; metabolism

The sirtuin proteins constitute class III histone deacetylases (HDACs). These evolutionarily conserved NAD(+)-dependent enzymes form an important component in a variety of cellular and biological processes with highly divergent as well as convergent roles in maintaining metabolic homeostasis, safeguarding genomic integrity, regulating cancer metabolism and also inflammatory responses. Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in promoting longevity and ameliorating age-associated pathologies. The contributions of other sirtuins in the field of aging are also gradually emerging. Here, we summarize some of the recent discoveries in sirtuins biology which clearly implicate the functions of sirtuin proteins in the regulation of premature cellular senescence and accelerated aging. The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms. Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.
Aging, Premature ; enzymology ; genetics ; Animals ; Humans ; Longevity ; genetics ; Sirtuin 1 ; genetics ; metabolism

Aging ; genetics ; metabolism ; Animals ; Diabetes Mellitus ; enzymology ; metabolism ; Humans ; Longevity ; genetics ; physiology ; Neoplasms ; enzymology ; metabolism ; Neurodegenerative Diseases ; enzymology ; metabolism ; Obesity ; enzymology ; metabolism ; Sirtuins ; genetics ; metabolism

The human mitochondrial genome consists of approximate 1500 genes, among which 37 are encoded by the mitochondrial DNA (mtDNA) and the remainder encoded in the nuclear DNA (nDNA). The mitochondria produces large amount of the cellular reactive oxygen species (ROS). ROS induces the mutations of mtDNA and mtDNA, which are associated with a wide range of age-related diseases including neurodegenerative diseases, cardiomyopathy, diabetes and various cancers.
Aging ; DNA, Mitochondrial ; genetics ; Genetic Therapy ; Humans ; Mitochondria ; genetics ; metabolism ; Mutation ; Neurodegenerative Diseases ; genetics ; therapy ; Reactive Oxygen Species ; metabolism

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

Down syndrome is caused by partial or complete triplication of genes located on chromosome 21. Its incidence increases dramatically with the age of women. Hypotheses proposed for this have included abnormal homologous recombination, defective spindle assembly, biological aging, reduction of cohesion complexes, endocrine disorders, oocyte selection model, and single nucleotide polymorphisms of genes that maintain chromosome stability, etc. A literature review is provided here.
Aging ; genetics ; Chromosomes, Human, Pair 21 ; genetics ; Down Syndrome ; genetics ; Female ; Humans ; Maternal Age ; Oocytes ; metabolism ; Polymorphism, Single Nucleotide ; genetics

The aim of the studies was to investigate klotho gene effect on the endothelial dysfunction of spontaneously hypertensive rats (SHR). In this study, ten SHR and ten normal Wistar rats, all 22 week old, were prepared. After given intraperitoneal anesthesia, the rats' brains, lungs, hearts, kidneys and aortas were removed. The identification was made by means of real-time polymerase chain reaction (Real-time PCR) and Enzyme-Linked Immunosorbent Assay (ELISA). Compared with the normal group, the klotho mRNA and protein in SHR were less than those in the control group with normal corresponding values, while Endothelin-1 (ET-1)'s mRNA and protein were more than those of normal group. The analysis of the correlation of mRNA and protein in heart and aorta revealed that klotho gene was negatively correlated to ET-1. The results showed that klotho significantly decreased in SHR, which might be influenced by hypertension-induced damage on the endothelial function.
Aging ; genetics ; Animals ; Endothelin-1 ; genetics ; metabolism ; Endothelium, Vascular ; physiopathology ; Glucuronidase ; genetics ; metabolism ; Hypertension ; genetics ; physiopathology ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR

The klotho gene was originally identified as a putative age-suppressing gene in mice that extends life span when overexpressed. It induces complex phenotypes resembling human premature aging syndromes when disrupted. The gene was named after a Greek goddess Klotho who spun the thread of life. Since then, various functional aspects of the klotho gene have been investigated, leading to the identification of multiple novel endocrine axes that regulate various metabolic processes and an unexpected link between mineral metabolism and aging. The purposes of this review were to overview recent progress on Klotho research and to discuss a novel aging mechanism.
Aging/genetics/*metabolism ; Animals ; Chronic Disease ; Fibroblast Growth Factors/metabolism ; Glucuronidase/genetics/*metabolism ; Homeostasis ; Humans ; Kidney Diseases/metabolism/physiopathology ; Phenotype ; Phosphates/metabolism ; Phosphorus, Dietary/metabolism ; *Signal Transduction

Aging ; genetics ; Embryo Research ; ethics ; Embryo, Mammalian ; metabolism ; Fertilization in Vitro ; Humans ; Morals ; Preimplantation Diagnosis ; RNA Editing ; genetics ; Zygote ; metabolism

The p66Shc gene has emerged as a novel gerontogene affecting health and life during aging. In murine models of aging,a genetic deficiency of the p66Shc gene,which encodes a phosphotyrosine signal adapter protein,extends life span by 30%. p66Shc is a crucial regulator of reactive oxygen species levels and is involved in age-related dysfunctions. UP to now,oxidative stress has been recognized to be involved in human diseases such as high cholesterol,diabetes,and cardiovascular diseases. Further study on the role of p66Shc will facilitate the research of novel disease-targetted drugs and slow down or cure age-related pathologies.
Aging ; genetics ; Animals ; Humans ; Longevity ; genetics ; Mice ; Oxidative Stress ; physiology ; Reactive Oxygen Species ; metabolism ; Shc Signaling Adaptor Proteins ; genetics