Abstract:Aging: old question, new challenge

Abstract:Aging occurs with cell beginning to lose function in a variety of cell types. If it takes place in a given tissue or organ prematurely ahead of other tissues and organs, it causes pathological development of diseases. How to treat aging cells and associated molecules is a challenge in anti-aging research. It has been demonstrated recently that aging occurs under physiological conditions during embryonic development of mammals, and that to some life forms aging never occurs. Involved in diverse diseases, aging is difficult to be measured and does not have universal markers. It is thus essential to comprehend the types of cells that undergo aging in human diseases and thereby the underlying molecular mechanisms. This article discusses recent research advances including: (1) The concept, classification and relevant mechanisms of cell aging; (2) Physiological aging: Developmentally programmed senescence; (3) Tissue homeostasis and aging; (4) Cell replicative senescence and related diseases: telomeres and cancer prognosis, idiopathic pulmonary fibrosis, hypertension; (5) Non-replicative cell aging and related diseases: Parkinson disease and diabetes; (6) Species diversity in aging and longevity.

Abstract:Tissue and organ-specific adult stem cells degenerate progressively with age, resulting in compromised tissue homeostasis and occurrence of aging-associated diseases. Epigenetic mechanisms play a key role in controlling individual as well as stem cell aging by the regulation of global and/or specific gene expression. Here, we summarize the recent findings on how epigenetic modifications especially DNA methylation and histone modifications regulate stem cell fate during aging, which may open a promising avenue towards achieving the goal of healthy aging.

Abstract:Stem cell ageing has been considered as one of the major causes of the declined regenerative capacity of tissues and organs with age, especially those with high proliferate cellular turnover. Growing evidences show that the ageing of the immune system is initiated at the very top of the hematopoietic hierarchy and the ageing of hematopoietic stem cell (HSC) directly affect the function of the immune system. However, molecule mechanisms underlies HSC ageing is still unclear. In this review, we summarize the phenotypes of ageing HSCs and discuss how the cell-intrinsic and cell-extrinsic mechanisms of HSCs ageing.

Abstract:Healthy aging not only benefits every individual, it is also useful to meet the challenge of the upcoming aging society. This requires mechanistic studies of how aging occurs. Mitochondria are the most important organelle for energy production, free radical metabolism and programmed cell death. Damaged and dysfunctional mitochondria are selectively removed by a mechanism of mitochondrial autophagy or mitophagy to protect the cells from excessive oxidative stress. The defective mitochondrial quality control may be closely link with aging. Caloric restriction and physical exercise stimulate both general autophagy and selective mitophagy. These will improve mitochondrial function and hugely benefit healthy aging.

Abstract:Aging causes a general decline in physiological function that leads to various metabolic and cardiovascular diseases. The links between aging and aging-associated diseases remain to be fully established，but recent studies demonstrate that suppressing the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway extends longevity and delays aging-associated metabolic and neurodegenerative diseases. As a key regulator of metabolism and aging，the mTOR signaling pathway has now become a hot spot for the development of effective therapeutic treatment for aging and aging-related diseases.

Abstract:Cellular senescence is a terminal growth arrest in the G1 phase of the cell cycle, featuring characteristic morphological, biochemical, and epigenetical changes. Cellular senescence results from telomere erosion, DNA damage, hypoxia, or oncogene deregulation, and it is one of main barriers of tumorigenesis. Proto-oncogene c-Myc encodes a transcription factor that can regulate the transcription of many genes, thereby affects different biological processes such as the cell cycle progression, senescence, apoptosis, metabolism, and so on. The c-Myc protein is closely related to cellular senescence, and it has abilities to affect cellular senescence-associated genes (hTERT, p16, p53, Bmi-1 and p27) transcription. The activation of c-Myc not only inhibits replicative senescence, but also can inhibit oncogene-induced senescence. The c-Myc suppresses Ras-induced cellular senescence with help with CDK2. The inactivation of c-Myc induces senescence in untransformed cells(such as human fibroblasts) as well as in many tumor cells. However, similar to ras gene, under certain conditions, c-Myc can induce cell senescence, and contributes to WRN gene-deficient cells senescence.

Abstract:microRNAs (miRNAs) are a class of endogenous non-coding RNAs with about 22 nucleotides. miRNAs are widely expressed in eukaryote and can post-transcriptionally control genes expression by blocking translation or inducing degradation through partial base-pair complementarity with their target mRNAs. Recent findings show that miRNAs are essential for lifespan determination in Caenorhabditis elegans (C. elegans), Drosophila, mice and human by targeting many aging related pathways. In this review, we summarize the recent literatures on various regulatory roles of miRNAs during aging. We introduce the pathways that function in the aging process and highlight how certain miRNAs regulate aging and aging related diseases through these pathways at the levels of organism lifespan, tissue aging and cellular senescence. Finally, we discuss future perspectives on the study of the mechanisms by which miRNAs modulate aging processes.

Abstract:Using yeast, nematodes, fruit flies, mice and other model organisms, many studies have shown that cellular senescence closely associated with redox events．Intracellular level of GSSG is increasing along with aging, while GSH and NADPH levels decrease．Redox changes will directly affect protein function, especially redox-sensitive cysteine-containing proteins, and further affect signal transduction and cell fate．Redox imbalance may be an important factor in aging process．In this review, we will summarize the latest progress in aging concerning redox balance, redox signal transduction and oxidative damage, and discuss new strategies in anti-aging and healthy aging, such as maintenance of redox balance, systemic regulation of redox status and individual redox treatment．

Abstract:Vascular aging has attracted curiosity and excited imagination throughout the history of humankind. This review focuses on structural and functional changes that occur in the vasculature during aging, as well as the novel founding mechanisms, with special emphasis on extracellular matrix alterations, endothelial progenitor cells endothelial exhaustion, senescence/dysfunction, and altered intercellular communication.

Abstract:Aging is a process of gradual functional decline accompanied with increased mortality rate. Using model organisms, researchers have demonstrated that aging is modulated by highly conserved signaling pathways, and genetic or environmental modulations can lead to significantly extended life span and delayed functional decline. Many exciting discoveries on the molecular mechanisms of aging were initially made in C. elegans, which is a great system for biology research because of the ease of genetic analysis and the conservation with higher species. Here we review the progress in aging research using C. elegans as a model. We focus on the highly conserved insulin/insulin-like growth factor 1 signaling (IIS) and target of rapamycin (TOR) pathway, as well as prospects for future studies.