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1.
Lara Feulner Hamed S. Najafabadi Simon Tanguay Janusz Rak Yasser Riazalhosseini 《Urologic oncology》2019,37(2):166-175
Background
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.Methods
Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.Results
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.Conclusion
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment. 相似文献2.
Alessia Pascale Marialaura Amadio Stefano Govoni Fiorenzo Battaini 《Pharmacological research》2007,55(6):560-569
The brain represents the primary centre for the regulation and control of all our body activities, receiving and interpreting sensory impulses and transmitting information to the periphery. Most importantly, it is also the seat of consciousness, thought, emotion and especially memory, being in fact able to encode, store and recall any information. Memory is really what makes possible so many of our complex cognitive functions, including communication and learning, and surely without memory, life would lose all of its glamour and purpose. Age-associated mental impairment can range in severity from forgetfulness at the border with pathology to dementia, such as in Alzheimer's disease. In recent years, one of the most relevant observations of research on brain aging relates to data indicating that age-related cognitive decline is not only due to neuronal loss, as previously thought; instead, scientists now believe that age-associated functional changes have more to do with the dysfunctions occurring over time. Within this context a prominent role is certainly played by signal transduction cascades which guarantee neuronal cell to elaborate coordinated responses to the multiple signals coming from the outside and to adapt itself to the environmental changes and requests. This review will focus the attention on protein kinase C pathway, with a particular interest on its activation process, and on the role of protein-lipid and protein-protein interactions to selectively localize the cellular responses. Furthermore, information is emerging and will be discussed on the possibility of mRNA stabilization through PKC activation. This review will also approach the issue on how alterations of these molecular cascades may have implications in physiological and pathological brain aging, such as Alzheimer's disease. 相似文献
3.
M G Van Luijtelaar F G Wouterlood J A Tonnaer H W Steinbusch 《Synapse (New York, N.Y.)》1991,8(3):162-168
Degeneration of neurons in the central nervous system is associated with morphological changes. Previous observations made at the light microscopical level indicated degeneration of serotonin-immunoreactive (IR) fibers in the aged rat brain. In this study, a comparison at the ultrastructural level was made between serotonin-IR normal thin and aberrant swollen varicose fibers in the caudate-putamen complex of the aged rat. Ultrastructural features such as the size and content of the thin varicose fibers resembled those in the caudate-putamen complex of the young rat as reported by others. The aberrant profiles were swollen, reaching a size of 6 microns. Their vesicles varied in size and were no longer uniformly round. Moreover, distorted mitochondria and membrane-filled vacuolelike structures were a common feature of the aberrant profiles. These changes are indicative of a degenerative process and give further evidence that, whereas many serotonergic fibers are preserved at high age, other serotonergic fibers are degenerating in the caudate-putamen complex of the aged rat. 相似文献
4.
神经节苷酯对老年性学习记忆减退鼠空间学习记忆能力的影响 总被引:4,自引:2,他引:2
目的研究神经节苷酯对老年性学习记忆减退鼠空间学习记忆的影响。方法用Moris水迷宫筛选老年性学习记忆减退昆明小鼠,腹腔注射神经节苷酯14天,然后测试小鼠定位航行和空间探索能力。结果与老年学习记忆减退鼠对照组比较,治疗组平均逃避潜伏期缩短,原平台游泳距离和穿环数次却增大,但均未达到老年学习记忆正常组和青年组水平。结论提示神经节苷酯可改善老年性学习记忆减退鼠空间学习记忆能力。 相似文献
5.
Mario González-Ulloa 《Aesthetic plastic surgery》1990,14(1):53-57
The author describes his surgical approach to the problems of the aging upper arm and elbow region. Surgery at an appropriate age can prevent the progressive wrinkling of the elbow which is further aggravated by aging of the upper arm. The author's operation is aimed at correcting both portions of the arm anatomy at the same time. 相似文献
6.
为探讨年龄增长及伴随的一些生理性变化对心脏径限的影响,对300余例20—81岁(平均46±16岁)的正常成人进行了超声心动图研究。多元逐步回归及协方差分析表明,左室壁厚度随年龄俱增,而左室舒张未期内径变化不大;室间隔/左室后壁厚度比值亦渐有增长,反映了室间隔的随龄增长稍快于左室后壁,故在增龄过程中,左室流出道稍有缩小;左房、主动脉根部和右室内径均有随年龄而增长的变化。二尖瓣舒张期 EF 斜率随年龄增长渐有下降,可能反映了左室顺应性的降低及二尖瓣弹性的减退。此外,一些心脏测值有性别差异,不少径限尚与体格大小或血压水平有相关关系。对于不同年龄组间心脏径限差异的原因,以及心脏径限彼此间的关系进行了分析和讨论,认为在临床上评价心脏径限正常与否和异常程度时,应考虑年龄、性别、体格大小、血压等因素的影响。 相似文献
7.
Reviewing the definition of "elderly" 总被引:1,自引:0,他引:1
Hajime Orimo Hideki Ito Takao Suzuki Atsushi Araki Takayuki Hosoi Motoji Sawabe 《Geriatrics & Gerontology International》2006,6(3):149-158
Conventionally, "elderly" has been defined as a chronological age of 65 years old or older, while those from 65 through 74 years old are referred to as "early elderly" and those over 75 years old as "late elderly." However, the evidence on which this definition is based is unknown. We have attempted to review the definition of elderly by analyzing data from long-term longitudinal epidemiological studies, and clinical and pathological studies that have been accumulated at the Tokyo Metropolitan Geriatric Hospital and the Tokyo Metropolitan Institute of Gerontology. Our recommendation might be a starting point in developing a strategy for a successful society by reviewing the definition of elderly based on comprehensive evidence in all aspects of social, cultural and medical sciences. 相似文献
8.
R. B. Biggs R. M. Hanley P. R. Morrison F. W. Booth 《Mechanisms of ageing and development》1991,60(3):285-293
The concentration of mitochondria decrease in the heart as rodents age from maturity to senescence. The reason for this change is not known. One purpose of the present study was to determine if cytochrome c mRNA, representative of proteins of the inner mitochondrial membrane, decreased in the hearts of Fischer 344 rats as they aged from 12 to 24 months. Twenty-two percent less cytochrome c mRNA existed per given quantity of extracted RNA from the heart in 24-month-old rats as compared with the 12-month-old group. No change in the quantities of cardiac -actin mRNA, Ca2+/calmodulin protein kinase II mRNA or 18S rRNA was noted between 12- und 24-month-old hearts. Thus, the decrease in cytochrome c mRNA suggests that decreased in mRNAs for proteins of the inner mitochondrial membrane could play some role in the diminished concentration of mitochondria that exists in the senescent heart. 相似文献
9.
M. S. Levine A. M. Adinolfi R. S. Fisher C. D. Hull D. Guthrie N. A. Buchwald 《Brain research》1988,440(2):267-279
These studies provide information on the changes in the ultrastructure in the caudate nucleus of aged cats. The major findings was that there was a decrease in the density of synapses in caudate neuropil. This decrease occurred in animals after 3 years of age and remained relatively constant in older animals. In conjunction with this change a population of unusually long synapses also occurred. These larger synaptic appositions were associated with enlarged spine heads. The caudate also showed a number of qualitative ultrastructural alterations. Many neurons contained accumulations of lipofuscin or lipopigment granules in aged animals. These inclusions occurred in both soma and dendrites of neurons and all types of glial cells. A unique configuration of collapsed agranular cisterns also was observed in aged animals. The present results indicate that decreases in synaptic density may by one morphological event underlying functional alterations observed in caudate neurons in aged cats. 相似文献
10.
The syndrome of senile gait 总被引:1,自引:0,他引:1
Summary Infrared computed stroboscopic photometry was used to quantify the kinematic profiles of walking in 10 elderly patients with symmetrical neurological disturbances of gait and in 19 age-matched neurologically healthy people. Clinical examination of the patients revealed similar profiles of walking even though their diagnoses were vascular dementia (2), normal pressure hydrocephalus (2), Alzheimer dementia with possible normal pressure hydrocephalus (2), mixed Alzheimer and vascular dementia (1), peripheral neuropathy (1), Alzheimer dementia with parkinsonian features (1), and un determined (1). Quantitatively, the patients' gait kinematics deviated greatly from control values, but these deviations were statistically attributable to reductions in stride. We suggest that many gait disturbances in elderly people are similar, regardless of etiology, because the characteristics of these gait disturbances are heavily veiled by nonspecific stride-dependent changes that comprise the syndrome of senile gait. 相似文献