A synopsis on aging—Theories,mechanisms and future prospects

Answering the question as to why we age is tantamount to answering the question of what is life itself. There are countless theories as to why and how we age, but, until recently, the very definition of aging – senescence – was still uncertain. Here, we summarize the main views of the different models of senescence, with a special emphasis on the biochemical processes that accompany aging.Though inherently complex, aging is characterized by numerous changes that take place at different levels of the biological hierarchy. We therefore explore some of the most relevant changes that take place during aging and, finally, we overview the current status of emergent aging therapies and what the future holds for this field of research.From this multi-dimensional approach, it becomes clear that an integrative approach that couples aging research with systems biology, capable of providing novel insights into how and why we age, is necessary.     

Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes.     

Caenorhabditis elegans--a paradigm for aging research: advantages and limitations.

In 1967, as we became interested in the biology of aging, we were faced with the following basic biological paradox: organisms are endowed with the capacity to detect and repair damage encountered at the molecular and cellular levels and yet functional capacity declines with time. In accordance with Strehler's suggestion (Time, Cells, and Aging, 2nd ed., Academic Press, New York, 1962), we adopted the basic premise that the underlying mechanisms of aging are common to all multi-cellular organisms. A search for a suitable experimental organism that fulfills the basic criteria for an appropriate model for aging research (Exp. Gerontol. 5 (1970) 7; Mech. Ageing Dev. 117 (2000) 21) led us to the selection of nematodes as a model for our initial series of experiments. Nematodes have thus been used in aging research for three decades. This review critically examines the major merits and shortcomings of this model organism for aging research and argues for greater appreciation of the need to understand the biology of the nematode life cycle not only as it is maintained in the laboratory, but also as it evolved and lives in nature.     

构建骨质疏松动物模型建模方法的改进及评价

BACKGROUND: Animal models of osteoporosis play an important role in the research of the pathogenesis, occurrence and development of osteoporosis, as well as in the clinical diagnosis, prevention and treatment of osteoporosis.   OBJECTIVE: To summarize and discuss the establishment and research ideas of osteoporosis models, explore the current situation and advance of osteoporosis models, compare the advantages and disadvantages of various methods, and provide evidence for clinical investigation. METHODS: A computer-based online search was conducted in SinoMed, VIP, Wanfang and PubMed databases by using the key words of “animal model, osteoporosis” from January 1969 to October 2015. The language was limited to both Chinese and English. Relevant articles were screened according to inclusion and exclusion criteria. The documents about the methods of osteoporosis model preparation, method improvement as well as their advantage and disadvantage were summarized. RESULTS AND CONCLUSION: A total of 576 articles were included. Among them, articles published earlier, duplicated, and similarly were excluded, and 53 articles were finally included. Various animal models of osteoporosis may only focus on the certain causes, certain stage, some of the main symptoms and some pathophysiological changes of disease. Accordingly, appropriate modeling methods and experimental animals should be selected based on research objective. Rat undergoing castration is the most commonly used model in the modeling of osteoporosis. Among drug methods for constructing osteoporosis model, glucocorticoids is the most commonly used one. Disuse method and nutritional method have limitations, and always combined with castration and drug methods. The effects of gene transfer, gene mutation and brain-derived model deserve further investigation.       

p63 deficiency activates a program of cellular senescence and leads to accelerated aging

The p53 tumor suppressor plays a key role in organismal aging. A cellular mechanism postulated to drive the aging process is cellular senescence, mediated in part by p53. Although senescent cells accumulate in elderly individuals, most studies have relied on correlating in vitro senescence assays with in vivo phenotypes of aging. Here, using two different mouse models in which the p53-related protein p63 is compromised, we demonstrate that cellular senescence and organismal aging are intimately linked and that these processes are mediated by p63 loss. We found that p63(+/-) mice have a shortened life span and display features of accelerated aging. Both germline and somatically induced p63 deficiency activates widespread cellular senescence with enhanced expression of senescent markers SA-beta-gal, PML, and p16(INK4a). Using an inducible tissue-specific p63 conditional model, we further show that p63 deficiency induces cellular senescence and causes accelerated aging phenotypes in the adult. Our results thus suggest a causative link between cellular senescence and aging in vivo, and demonstrate that p63 deficiency accelerates this process.     

A review of successful aging models: proposing proactive coping as an important additional strategy

Successful aging is an important concept, and one that has been the subject of much research. During the last 15 years, the emphasis of this research has shifted from formulating criteria for successful aging to describing the processes involved in successful aging. The main purpose of the present article is to review psychological models of successful aging. The model of Selective Optimization with Compensation (SOC-model) proves to be one of the leading models in this field. Although evidence about its value is accumulating, we argue that this model mainly focuses on how people react to losses and that proactive coping aimed at preventing potential threats to goals may also be a valuable strategy. We propose that proactive coping may be important for successful aging, since it results in a prolonged availability of resources for optimization and compensation processes and a delay in disengagement from important goals.     

Replicative senescence: a critical review

Human cells in culture have a limited proliferative capacity. After a period of vigorous proliferation, the rate of cell division declines and a number of changes occur in the cells including increases in size, in secondary lysosomes and residual bodies, nuclear changes and a number of changes in gene expression which provide biomarkers for senescence. Although human cells in culture have been used for over 40 years as models for understanding the cellular basis of aging, the relationship of replicative senescence to aging of the organism is still not clear. In this review, we discuss replicative senescence in the light of current information on signal transduction and mitogenesis, cell stress, apoptosis, telomere changes and finally we discuss replicative senescence as a model of aging in vivo.     

Hybrid Research Models: Natural Opportunities for Examining Mental Health in Context

The articles in this series promote hybrid research models to bridge the gap between efficacy and effectiveness. We suggest that efforts such as those described in these articles are long overdue. Given the enormous public health consequences of the lack of available and effective mental health services, we no longer can afford research that neglects the natural state of affairs or that leaves others to translate research into practice. It is time to acknowledge that the process of testing interventions in the university for transfer to the community is neither efficient nor empirically justified. Guided by the articles in this series, we focus on the ways in which hybrid models can provide natural opportunities to advance the field and lead to a new generation of research that is both contextually relevant and methodologically rigorous. An iterative process of research and practice is proposed that can lead to stronger theories and methods and enhanced understanding of mental health in context.     

Advice to an aging scientist

Fifty years ago, Peter Medawar and George Williams developed two now-classic theories for the evolution of senescence. In the past 20 years, evolutionary biologists studying aging have developed explicit mathematical models of these theories, used these models to derive explicit predictions, and tested these predictions using a variety of approaches. But, we argue here, our singular focus on these models may have hindered progress in evolutionary studies of aging. Research in this area has not kept pace with dramatic advances in evolutionary theory and molecular genetics. Progress in evolutionary studies of aging will depend on a bold, integrative approach, incorporating evolutionary and molecular advances from other fields, along with the powerful statistical and mathematical tools now available. We discuss several specific examples where we may gain new insight into the causes of aging by looking to other evolutionary phenomena, including sexual conflict and the evolution of social behavior. In addition, we present new results which suggest that the analysis of gene networks may lend particular insight into the genetic underpinnings of the aging process.     

去势雌性山羊骨质疏松模型的特点

背景：加强骨质疏松模型的研究,对骨质疏松性骨折的防治非常必要。 目的：综述现有的山羊骨质疏松模型的特点,为骨质疏松和骨质疏松性骨折的防治提供帮助。 方法：应用计算机检索中国知网和PubMed数据库中2005-06/2011-02关于去势雌性山羊骨质疏松模型的文章,在标题和摘要中以“骨质疏松症、动物模型、山羊、卵巢切除”或“osteoporosis, animal model, goats, ovariectomy”为检索词进行检索。选择文章内容与建立骨质疏松模型的方法、评价标准,骨质变化等有关的研究,排除重复研究及建立雄性动物骨质疏松模型的研究。 结果与结论：初检得到48 篇文献,根据纳入标准选择21篇文章进行综述。山羊来源方便,容易处置,具有自动排卵和与成年妇女相似的排卵周期,是理想的实验动物材料;能获取大量血、尿和骨骼标本,是理想的制备骨质疏松模型的实验动物。去势法是建立骨质疏松模型常用的方法,山羊骨质疏松模型的建立将为骨质疏松和骨质疏松性骨折防治药物的开发、改进内置物设计等提供研究的基础。 关键词：卵巢切除术;骨质疏松;模型;雌激素;骨代谢;山羊 doi:10.3969/j.issn.1673-8225.2012.07.038             

Factors influencing acceptance of technology for aging in place: A systematic review

PurposeTo provide an overview of factors influencing the acceptance of electronic technologies that support aging in place by community-dwelling older adults. Since technology acceptance factors fluctuate over time, a distinction was made between factors in the pre-implementation stage and factors in the post-implementation stage.MethodsA systematic review of mixed studies. Seven major scientific databases (including MEDLINE, Scopus and CINAHL) were searched. Inclusion criteria were as follows: (1) original and peer-reviewed research, (2) qualitative, quantitative or mixed methods research, (3) research in which participants are community-dwelling older adults aged 60 years or older, and (4) research aimed at investigating factors that influence the intention to use or the actual use of electronic technology for aging in place. Three researchers each read the articles and extracted factors.ResultsSixteen out of 2841 articles were included. Most articles investigated acceptance of technology that enhances safety or provides social interaction. The majority of data was based on qualitative research investigating factors in the pre-implementation stage. Acceptance in this stage is influenced by 27 factors, divided into six themes: concerns regarding technology (e.g., high cost, privacy implications and usability factors); expected benefits of technology (e.g., increased safety and perceived usefulness); need for technology (e.g., perceived need and subjective health status); alternatives to technology (e.g., help by family or spouse), social influence (e.g., influence of family, friends and professional caregivers); and characteristics of older adults (e.g., desire to age in place). When comparing these results to qualitative results on post-implementation acceptance, our analysis showed that some factors are persistent while new factors also emerge. Quantitative results showed that a small number of variables have a significant influence in the pre-implementation stage. Fourteen out of the sixteen included articles did not use an existing technology acceptance framework or model.ConclusionsAcceptance of technology in the pre-implementation stage is influenced by multiple factors. However, post-implementation research on technology acceptance by community-dwelling older adults is scarce and most of the factors in this review have not been tested by using quantitative methods. Further research is needed to determine if and how the factors in this review are interrelated, and how they relate to existing models of technology acceptance.     

Use of rodents as models for the study of “normal aging”: Conceptual and practical issues

Certain guidelines may exist for selecting and using rodent models for aging research. These are based, however, on only operational criteria because we presently lack good biomarkers for (or even a suitable definition of) normal aging. Longevity and disease characteristics of the experimental population are the most important of the operational criteria for choosing a particular rodent model. These factors, in turn, are influenced by genetics and by environmental factors, including diet, housing, and physical activity.     

建立股骨头坏死动物模型的最新信息

背景：在临床骨科研究方面,为了研究股骨头坏死的病因及发病机制,从根本上进行治疗,出现了各种各样的股骨头坏死的动物模型。 目的：对近几年来学者们建立的各种各样股骨头坏死的改良模型作一个综述,分析各种模型的优劣,用来指导临床对股骨头坏死发病机制进行研究或者评价一种新的治疗方法的临床价值。 方法：以“股骨头坏死;动物模型”或“femoral head necrosis; animal model”为检索词检索CNKI中国知网数据库和PubMed数据库中2005年1月至2011年12月关于建立股骨头坏死动物模型的相关文献136篇,根据纳入标准选择20篇文章进行分析。 结果与结论：目前采用最多的建模方法是改良激素型,但是不同的造模方法都有其自己的优缺点,动物模型的建立方法的选择,应该与自己实验目的紧紧相连。无论是为了病因及发病机制研究,还是治疗效果的评价,建立动物模型的方法都还需要进一步完善。     

Grading score system: A method for evaluation of the degree of senescence in Senescence Accelerated Mouse (SAM)

For evaluation of the degree of senescence in SAM-P, accelerated senescence prone mouse, formerly called SAM or prone series or P-series, consisting of SAM-P/1, SAM-P/2, SAM-P/3 and SAM-P/4 corresponding to P-1, P-2, P-3 and P-4 series, respectively, in the previous reports, and in SAM-R, accelerated senescence resistant mouse, formerly called resistant series or R-series, consisting of SAM-R/1, SAM-R/2 and SAM-R/3 corresponding to R-1, R-2 and R-3 series, respectively, in the previous reports, the grading score system was adopted. The items to be examined in this system include 11 categories selected from the clinical signs and gross lesions considered to be associated with the aging process. The degree of the senescence in each category was graded from 0 to 4 according to the detailed criteria devised in our laboratory. After 8 months of age each mouse was examined every 4 months, and some of the mice were examined after 2 months of age.In almost all categories, the grading score and incidence began to increase from 4 or 6 months of age and continued to increase with advancing age in both SAM-P and SAM-R. The increase, however, was more marked in SAM-P than in SAM-R. The slow but steady increase in the SAM-R levelled out at 24 months of age and was comparable to that of 12 months of age in SAM-P. In both SAM-P/1 at 8 months of age and SAM-R/2 at 12 months of age, there was a significant reverse correlation between total score of this grading score system and length of residual life after examination.Systematic and extensive studies using the grading score system showed that if the validity of the system is, based on “irreversibility” and “universality” of the changes in     

An altered response in the induction of cell membrane (Na + K)ATPase by thyroid hormone is characteristic of senescence in cultured human fibroblasts

There have been numerous investigations of thyroid function during senescence in humans. However, very little information is available on thyroid hormone action at the cell level during senescence. Therefore, we have investigated thyroid hormone induction of cell membrane (Na + K)ATPase during human senescence using three experimental fibroblast cell culture systems: (1) cells from premature aging syndrome, progeria; (2) aging in vitro; and (3) early passage cells from aged patients. In all cases senescence is associated with a dramatic alteration from the normal dose-dependent thyroid hormone induction of (Na + K)ATPase. Senescent cells depleted of thyroid hormones demonstrated an elevated activity of (Na + K)ATPase, while non-senescing cells exhibit the characteristic basal enzyme activities in the hypothyroid state. These results indicate that human senescence is associated with extreme alterations in thyroid hormone regulation of (Na + K)ATPase; and may suggest a more general change in thyroid hormone action at senescence. These changes may be associated with important alterations in cell metabolism and intracellular ionic environment during senescence.     

腰椎间盘突出症蛋白质组学变化与中医证型的相关性

背景：腰椎间盘突出症的中西医结合治疗效果较好。 目的：全面综述腰椎间盘突出症中医辨证分型与蛋白质组学相关的研究。 方法：检索万方、清华同方等中文数据库及Pubmed数据库2001-01/2010-12的相关文章,中文检索词为“中医证型、蛋白质组学、腰椎间盘突出症”,英文检索词为“syndrome types, traditional Chinese medicine, protcomics, lumbar intervertebral disk protrusion”。纳入腰椎间盘突出症血清蛋白质组学研究及蛋白质组学、中医分型与中医药3者关联的研究,排除重复研究及Meta分析类文章。 结果与结论：计算机检索得到361篇文献,中文79篇,英文282篇,阅读标题与摘要进行筛选,排除与此文无关的文献。对29个符合要求的研究进行综述。研究认为,部分疾病的中医分型与血清蛋白质组学有关,机体某些特异性标志蛋白表达可能与椎间盘退变相关。腰椎间盘突出症与中医血瘀证、湿热证、寒湿证等证型的关联性得到了部分实验及临床的验证,但缺乏蛋白质组学相关性研究。