不同月龄大鼠血清IL-2、IL-4、IL-6含量比较

目的：比较不同月龄大鼠免疫功能及抗氧化能力的差异。方法：选择15、25月龄健康雄性SD大鼠各10只，以3月龄青年鼠10只为对照组。采用放免法测定血清白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)含量，并计算大鼠胸腺体重指数；采用化学法检测血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活力，丙二醛(MDA)含量。结果：衰老大鼠胸腺体重指数及IL-2、IL-4明显下降，IL-6水平升高SOD、GSH-PX活力下降，MDA含量增高，并且变化与月龄有关。结论：不同月龄大鼠衰老状况各有特点，不同年龄阶段应采用不同方法延缓衰老。     

卡托普利对心脏成纤维细胞端粒长度的作用研究

目的探讨卡托普利对心脏成纤维细胞端粒长度的影响。方法使用流式荧光原位杂交法（Flow—Fish）检测成纤维细胞端粒长度的变化。结果经过卡托普利处理过的成纤维细胞端粒明显缩短。结论本研究通过Flow—Fish法证实了卡托普利能缩短成纤维细胞端粒的长度，引起心脏成纤维细胞衰老的发生，从而抑制CFs的增殖。     

肾虚衰老理论研究的新思路

在中医学中,肾虚衰老一直占主导地位,而生命科学研究则表明机体生长、发育与衰老的基础是以细胞周期为核心的细胞增殖、分化与衰老等生命活动,两者之间必然有着某种本质的联系,将肾虚衰老、肾藏精、肾为先天之本理论与细胞基本生命活动之一的"细胞衰老"结合研究,可进一步揭示肾虚衰老理论的本质以及补肾防衰老的分子机制,同时可从另一个角度揭示目前尚未知的中医肾本质,从而深化中医学肾为先天之本理论.     

人参皂苷Rg1抗衰老作用可能与改变p16、cyclin D、CDK4的表达有关

目的 :探讨人参皂苷Rg1对抗三丁基过氧化氢 (t BHP)诱导的WI 38细胞衰老作用及其可能细胞周期调控机制。方法 :将WI 38细胞随机分为 4组 ,用不同剂量Rg1预处理。从 30代开始 ,隔代用t BHP作用 ,每次 1h ,共 4次 ,诱导细胞衰老。从光镜、透射电镜观察细胞形态及超微结构 ;流式细胞术分析G1期细胞比例 ;以及SA β 半乳糖苷酶的细胞化学染色 ,确定Rg1的抗衰老作用。并采用免疫印迹技术对CDK4、cyclinD1和p16等表达情况进行检测。结果 :Rg1预处理组与单纯t BHP处理组相比 ,细胞形态体积小、胞体不如后者扁平 ,次级溶酶体减少 ,G1期细胞比例下降 ,SA β 半乳糖苷酶染色阳性细胞百分比下降 ,说明Rg1在t BHP诱导细胞衰老模型中有抗衰老作用。进一步发现用Rg1预处理后 ,p16、cyclinD1表达水平降低、CDK4表达水平增加。结论 :提示Rg1可能通过改变细胞周期调控因子的表达而发挥其抗t BHP诱导的WI 38细胞衰老作用。     

Relation Between Cellular Senescence and Liver Diseases

Cellular senescence refers to a process that cellular proliferation and differentiation modulated by the multiple stimulating factors gradually decline.Aging cells present the irreversible stop of proliferation and differentiation and change in secretory function because the cell cycle of aging cells is steadily blocked at some point. It has have been shown that cellular senescence plays an important role in the occurrence and development of liver diseases. In this paper, we review the advances in relations between cellular senescence and liver diseases.     

The role of myeloid-derived suppressor cells (MDSC) in the inflammaging process

A chronic low-grade inflammation is one of the hallmarks of the aging process. This gradually augmenting inflammatory state has been termed inflammaging. Inflammaging is associated with increased myelopoiesis in the bone marrow. This myelopoiesis-biased process increases the generation not only of mature myeloid cells, e.g. monocytes, macrophages, and neutrophils, but also immature myeloid progenitors and myeloid-derived suppressor cells (MDSCs). It is known that the aging process is associated with a significant increase in the presence of MDSCs in the bone marrow, blood, spleen, and peripheral lymph nodes. Consequently, MDSCs will become recruited into inflamed tissues where they suppress acute inflammatory responses and trigger the resolution of inflammation. However, if the perpetrator cannot be eliminated, the long-term presence of MDSCs suppresses the host’s immune defence and increases the susceptibility to infections and tumorigenesis. Chronic immunosuppression also impairs the clearance of waste products and dead cells, impairs energy metabolism, and disturbs tissue proteostasis. This immunosuppressive state is reminiscent of the immunosenescence observed in inflammaging. It seems that proinflammatory changes in tissues with aging stimulate the myelopoietic production of MDSCs which subsequently induces immunosenescence and maintains the chronic inflammaging process. We will briefly describe the functions of MDSCs and then examine in detail how inflammaging enhances the generation MDSCs and how MDSCs are involved in the control of immunosenescence occurring in inflammaging.     

Akt inhibition improves irinotecan treatment and prevents cell emergence by switching the senescence response to apoptosis

Activated in response to chemotherapy, senescence is a tumor suppressive mechanism that induces a permanent loss of proliferation. However, in response to treatment, it is not really known how cells can escape senescence and how irreversible or incomplete this pathway is. We have recently described that cells that escape senescence are more transformed than non-treated parental cells, they resist anoikis and rely on Mcl-1. In this study, we further characterize this emergence in response to irinotecan, a first line treatment used in colorectal cancer. Our results indicate that Akt was activated as a feedback pathway during the early step of senescence. The inhibition of the kinase prevented cell emergence and improved treatment efficacy, both in vitro and in vivo. This improvement was correlated with senescence inhibition, p21waf1 downregulation and a concomitant activation of apoptosis due to Noxa upregulation and Mcl-1 inactivation. The inactivation of Noxa prevented apoptosis and increased the number of emergent cells. Using either RNA interference or p21waf1-deficient cells, we further confirmed that an intact p53-p21-senescence pathway favored cell emergence and that its downregulation improved treatment efficacy through apoptosis induction. Therefore, although senescence is an efficient suppressive mechanism, it also generates more aggressive cells as a consequence of apoptosis inhibition. We therefore propose that senescence-inducing therapies should be used sequentially with drugs favoring cell death such as Akt inhibitors. This should reduce cell emergence and tumor relapse through a combined induction of senescence and apoptosis.     

From the Cover: The age-specific force of natural selection and biodemographic walls of death

W. D. Hamilton’s celebrated formula for the age-specific force of natural selection furnishes predictions for senescent mortality due to mutation accumulation, at the price of reliance on a linear approximation. Applying to Hamilton’s setting the full nonlinear demographic model for mutation accumulation recently developed by Evans, Steinsaltz, and Wachter, we find surprising differences. Nonlinear interactions cause the collapse of Hamilton-style predictions in the most commonly studied case, refine predictions in other cases, and allow walls of death at ages before the end of reproduction. Haldane’s principle for genetic load has an exact but unfamiliar generalization.