人参皂苷Rg1对神经细胞衰老和衰老相关异染色质聚集的影响

目的探讨人参皂苷Rg1预处理对三丁基过氧化氢(t-BHP)诱导的神经细胞衰老及异染色质聚集(SAHF)的影响。方法常规培养Neuro-2a细胞株,在造模药物刺激前,给予不同剂量的人参皂苷Rg1,同时设置模型对照组、正常对照组。进行细胞活力检测、衰老相关半乳糖苷酶染色、衰老相关异染色质聚集检测。结果人参皂苷Rg1预处理可改善t-BHP诱导的细胞活力降低,此改善呈剂量依赖性;人参皂苷Rg1预处理各组,SA-β-gal染色细胞阳性数呈剂量依赖性降低;人参皂苷Rg1预处理可预防t-BHP诱导的SAHF形成,呈显著剂量依赖性。结论人参皂苷Rg1预处理可剂量依赖性地预防神经细胞衰老,防止异染色质聚集,有必要进一步研究。     

Anticancer activity of Kalanchoe tubiflora extract against human lung cancer cells in vitro and in vivo

Uncontrolled cell proliferation is a common feature of human cancer. Some of herbal extract or plant‐derived medicine had been shown as an important source of effective anticancer agents. We previously reported that an n‐BuOH‐soluble fraction of Kalanchoe tubiflora has antiproliferative activity by inducing mitotic catastrophe. In this study, we showed that the H₂O‐soluble fraction of Kalanchoe tubiflora (KT‐W) caused cell cycle arrest, and senescence‐inducing activities in A549 cells. We used 2 dimensional PAGE to analyze the protein expression levels after KT‐W treatment, and identified that the energy metabolism‐related proteins and senescence‐related proteins were disturbed. In vivo experiments showed that the tumor growths in A549‐xenografted nude mice were effectively inhibited by KT‐W. Our findings implied that KT‐W is a putative antitumor agent by inducing cell cycle arrest and senescence. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1663–1673, 2016.     

细胞早衰对放射性皮肤损伤中伤口愈合的影响及机制研究

医疗照射、职业性暴露、应急照射均可引起放射性皮肤损伤, 相关的研究大多集中在放射性皮肤损伤的预防与治疗措施方面, 但相关分子尚未完全阐明。研究表明, 辐射诱导的细胞早衰在放射性皮肤损伤发生发展中发挥重要作用。本文从放射性皮肤损伤机制及细胞早衰促进放射性皮肤损伤的发生发展, 电离辐射诱导的细胞早衰信号通路, 及细胞早衰在伤口愈合中的作用3个方面进行综述, 探讨辐射诱导的细胞早衰与放射性皮肤损伤的关系。     

Aging of schizophrenic patients as seen through the Rorschach test.

The authors have repeated, on the average 29.7 years later, Rorschach test in 11 schizophrenic men and 19 schizophrenic women. This work was carried out in the course of a follow-up study of schizophrenics more than 65 years of age. Analysis of the records showed that the only differences between the first and second examinations were increases in animal and popular responses in old age. The authors have tried to relate these findings to the general trends of schizophrenic development in senescence.     

Molecular genetic studies of cellular senescence

The limited doubling potential of normal cells in culture was first proposed as a model for cellular aging by Hayflick in 1961. This phenomenon of in vitro cellular senescence is now well documented for a number of different normal human cell types. In an attempt to determine whether random events or programmed genetic processes were responsible for cellular aging, we performed a series of cell fusion studies. We determined that hybrids from fusion of normal with immortal human cells had limited proliferative potential, indicating that senescence is a dominant phenotype. We exploited the fact that immortality was recessived to assign a large number of different immortal human cell lines to four complementation groups for indefinite division. More recently, we have determined that the introduction of a single normal human chromosome 4 into HeLa (cervical carcinoma) cells by microcell fusion induced senescence in this immortal line. The results of these whole cell and microcell fusion studies support the hypotheses that propose senescence results from active, genetic mechanisms.     

Diurnal variation in hepatic glutathione content as a function of age

The purpose of this study was to investigate the influence of aging on the diurnal varitaion in glutathione (GSH) content of mouse liver. Young (7 months) and old (27 months) C57BL mice were housed under standarized conditions with lighting from 0800 to 2000 and free access to food and water. GSH was determined in acid extracts of liver homogenates by HPLC separation and fluorometric detection of the o-phthaldialdehyde derivative. A diurnal rhythm in hepatic GSH concentration was evident in young and old mice of both sexes. Peak levels of GSH occurred at 1000 and were unaffected by age or gender; however, age and sex-dependent differences were observed in the lowest concentration of GSH and in the amplitude of the GSH cycle. Hepatic GSH levels at 2200 and 0600 were 30–35% lower in old males than in young males and 25–40% lower in young females than in young males. The results may provide an explanation for the inconsistencies in previous findings about the influence of aging on hepatic GSH concentrations. © 1992 Wiley-Liss, Inc.     

Re-expression of senescent markers in deinduced reversibly immortalized cells

We have developed a simian virus 40 (SV40) T-antigen immortalized human cell line, 1MR90-D305.2H4 (IDH4), in which the expression of T-antigen is controlled by the mouse mammary tumor virus (MMTV) promoter and thus regulated by steroids such as dexamethasone. Studies on the regulation of proliferation by T-antigen led to the formulation of a two-stage model for human cell immortalization, in which a mortality stage 1 mechanism (M1) was the target of T-antigen action, and an independent mortality stage 2 mechanism (M2) produced crisis and prevented T-antigen from directly immortalizing cells. Rarely, a cell expressing T-antigen escaped crisis (e.g., M2) and was capable of indefinite proliferation. This model predicted that the deinduction of T-antigen in IDH4 cells would lead to the reexpression of the M1 mechanism, and thus a reexpression of the senescent phenotype. Our study confirms the prediction that, in the absence of steroids, IDH4 cells express a variety of morphological and biochemical markers characteristic of normal senescent human fibroblasts.     

Life table tests of evolutionary theories of senescence

The phenomenon of senescence requires both evolutionary and proximate explanations. The most widely accepted evolutionary explanation for senescence is that it never gets exposed to natural selection because environmental hazards kill all individuals before the age at which senescence causes decreased fitness. If this explanation is sufficient, wild populations should not demonstrate senescence, and their mortality rates should therefore remain constant during adult life, except when environmental causes of mortality have recently decreased. The alternative explanation for the persistence of the genes that cause senescence is that they have been selected for because they have pleiotropic effects that are beneficial early in life when the force of selection is strongest. Where this is the case, mortality rates should increase with age in wild populations. A method is described for using life table data to calculate an estimate of the intensity of selection acting on senescence in wild populations. This method is applied to a variety of life tables. The results suggest that pleiotropic genes may be important causes of senescence in some populations, but not in others. This has implications for research on the proximate mechanisms of senescence.