• 主题
高级搜索  >
历史搜索 清空历史

您现在的位置：首页>美国卫生研究院文献>Aging Cell

期刊信息

  • 期刊名称：

    -

  • 刊频： Bimonthly
  • NLM标题： Aging Cell
  • iso缩写： -
  • ISSN： -

年度选择

更多>>

  • 排序：
  • 显示：
  • 每页：
全选（0）
<9/20>
共985条结果
  • 1.

    【2hr】Corrigendum

    包量

    机译 更正
    • 作者：
    • 刊名：Aging Cell
    • 2019年第3期
    摘要：
  • 2.

    【2hr】Depletion of B cells rejuvenates the peripheral B‐cell compartment but is insufficient to restore immune competence in aging

    包量

    机译 B细胞的枯竭使周围的B细胞区室恢复活力，但不足以恢复衰老的免疫能力
    摘要：Aging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B‐cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B‐cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B‐cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo. Additionally, elderly patients, previously treated with rituximab healthy elderly and young individuals, were vaccinated against hepatitis B (HBV) after undergoing a detailed analysis for B‐cell compartments. B‐cell depletion in old mice resulted in rejuvenated B‐cell population that was derived from de novo synthesis in the bone marrow. The rejuvenated B cells exhibited a "young"‐like repertoire and cellular responsiveness to immune stimuli in vitro. Yet, mice treated with B‐cell depletion did not mount enhanced antibody responses to immunization in vivo, nor did they survive longer than control mice in "dirty" environment. Consistent with these results, peripheral B cells from elderly depleted patients showed a "young"‐like repertoire, population dynamics, and cellular responsiveness to stimulus. Nevertheless, the response rate to HBV vaccination was similar between elderly depleted and nondepleted subjects, although antibody titers were higher in depleted patients. This study proposes a proof of principle to rejuvenate the peripheral B‐cell compartment in aging, through B‐cell depletion. Further studies are warranted in order to apply this approach for enhancing humoral immune responsiveness among the elderly population.
  • 3.

    【2hr】Molecular footprint of Medawar’s mutation accumulation process in mammalian aging

    包量

    机译 哺乳动物衰老过程中Medawar突变积累过程的分子足迹
    摘要：Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline mutations expressed in old age can drift to fixation and thereby lead to aging‐related phenotypes. Although widely cited, empirical evidence for this hypothesis has remained limited. Here, we test one of its predictions that genes relatively highly expressed in old adults should be under weaker purifying selection than genes relatively highly expressed in young adults. Combining 66 transcriptome datasets (including 16 tissues from five mammalian species) with sequence conservation estimates across mammals, here we report that the overall conservation level of expressed genes is lower at old age compared to young adulthood. This age‐related decrease in transcriptome conservation (ADICT) is systematically observed in diverse mammalian tissues, including the brain, liver, lung, and artery, but not in others, most notably in the muscle and heart. Where observed, ADICT is driven partly by poorly conserved genes being up‐regulated during aging. In general, the more often a gene is found up‐regulated with age among tissues and species, the lower its evolutionary conservation. Poorly conserved and up‐regulated genes have overlapping functional properties that include responses to age‐associated tissue damage, such as apoptosis and inflammation. Meanwhile, these genes do not appear to be under positive selection. Hence, genes contributing to old age phenotypes are found to harbor an excess of slightly deleterious alleles, at least in certain tissues. This supports the notion that genetic drift shapes aging in multicellular organisms, consistent with Medawar's mutation accumulation hypothesis.
  • 4.

    【2hr】Are skin senescence and immunosenescence linked within individuals?

    包量

    机译 个体内的皮肤衰老和免疫衰老是否相关？
    摘要：With advancing age, many organs exhibit functional deterioration. The age‐associated accumulation of senescent cells is believed to represent one factor contributing to this phenomenon. While senescent cells are found in several different organ systems, it is not known whether they arise independently in each organ system or whether their prevalence within an individual reflects that individual's intrinsic aging process. To address this question, we studied senescence in two different organ systems in humans, namely skin and T cells in 80 middle‐aged and older individuals from the Leiden Longevity Study. Epidermal p16INK4a positivity was associated with neither CD4+ nor CD8+ T‐cell immunosenescence phenotype composites (i.e., end‐stage differentiated/senescent T cells, including CD45RA+CCR7‐CD28‐CD27‐CD57+KLRG1+ T cells). Dermal p16INK4a positivity was significantly associated with the CD4+, but not with the CD8+ immunosenescence composite. We therefore conclude that there is limited evidence for a link between skin senescence and immunosenescence within individuals.
  • 5.

    【2hr】Transcriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults

    包量

    机译 对人类IL-7受体α低和高效应记忆CD8 + T细胞的转录组学分析揭示了与老年人流感疫苗反应相关的年龄相关特征
    摘要：Here, we investigated the relationship of the age‐associated expansion of IL‐7 receptor alpha low (IL‐7Rαlow) effector memory (EM) CD8+ T cells with the global transcriptomic profile of peripheral blood cells in humans. We found 231 aging signature genes of IL‐7Rαlow EM CD8+ T cells that corresponded to 15% of the age‐associated genes (231/1,497) reported by a meta‐analysis study on human peripheral whole blood from approximately 15,000 individuals, having high correlation with chronological age. These aging signature genes were the target genes of several transcription factors including MYC, SATB1, and BATF, which also belonged to the 231 genes, supporting the upstream regulatory role of these transcription factors in altering the gene expression profile of peripheral blood cells with aging. We validated the differential expression of these transcription factors between IL‐7Rαlow and high EM CD8+ T cells as well as in peripheral blood mononuclear cells (PBMCs) of young and older adults. Finally, we found a significant association with influenza vaccine responses in older adults, suggesting the possible biological significance of the aging signature genes of IL‐7Rαlow EM CD8+ T cells. The results of our study support the relationship of the expansion of IL‐7Rαlow EM CD8+ T cells with the age‐associated changes in the gene expression profile of peripheral blood cells and its possible biological implications.
  • 6.

    【2hr】Estrogen receptor α promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP/PS1 mice

    包量

    机译 雌激素受体α促进神经元细胞和APP / PS1小鼠中的Cav1.2泛素化和降解
    摘要：Cav1.2 is the pore‐forming subunit of L‐type voltage‐gated calcium channel (LTCC) that plays an important role in calcium overload and cell death in Alzheimer's disease. LTCC activity can be regulated by estrogen, a sex steroid hormone that is neuroprotective. Here, we investigated the potential mechanisms in estrogen‐mediated regulation of Cav1.2 protein. We found that in cultured primary neurons, 17β‐estradiol (E2) reduced Cav1.2 protein through estrogen receptor α (ERα). This effect was offset by a proteasomal inhibitor MG132, indicating that ubiquitin–proteasome system was involved. Consistently, the ubiquitin (UB) mutant at lysine 29 (K29R) or the K29‐deubiquitinating enzyme TRAF‐binding protein domain (TRABID) attenuated the effect of ERα on Cav1.2. We further identified that the E3 ligase Mdm2 (double minute 2 protein) and the PEST sequence in Cav1.2 protein played a role, as Mdm2 overexpression and the membrane‐permeable PEST peptides prevented ERα‐mediated Cav1.2 reduction, and Mdm2 overexpression led to the reduced Cav1.2 protein and the increased colocalization of Cav1.2 with ubiquitin in cortical neurons in vivo. In ovariectomized (OVX) APP/PS1 mice, administration of ERα agonist PPT reduced cerebral Cav1.2 protein, increased Cav1.2 ubiquitination, and improved cognitive performances. Taken together, ERα‐induced Cav1.2 degradation involved K29‐linked UB chains and the E3 ligase Mdm2, which might play a role in cognitive improvement in OVX APP/PS1 mice.
  • 7.

    【2hr】Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus

    包量

    机译 海马神经干细胞的表型和功能异质性
    摘要：Adult neurogenesis persists in the hippocampus of most mammal species during postnatal and adult life, including humans, although it declines markedly with age. The mechanisms driving the age‐dependent decline of hippocampal neurogenesis are yet not fully understood. The progressive loss of neural stem cells (NSCs) is a main factor, but the true neurogenic output depends initially on the actual number of activated NSCs in each given time point. Because the fraction of activated NSCs remains constant relative to the total population, the real number of activated NSCs declines in parallel to the total NSC pool. We investigated aging‐associated changes in NSCs and found that there are at least two distinct populations of NSCs. An alpha type, which maintains the classic type‐1 radial morphology and accounts for most of the overall NSC mitotic activity; and an omega type characterized by increased reactive‐like morphological complexity and much lower probability of division even under a pro‐activation challenge. Finally, our results suggest that alpha‐type NSCs are able to transform into omega‐type cells overtime and that this phenotypic and functional change might be facilitated by the chronic inflammation associated with aging.
  • 8.

    【2hr】α‐Synuclein toxicity in yeast and human cells is caused by cell cycle re‐entry and autophagy degradation of ribonucleotide reductase 1

    包量

    机译 酵母和人类细胞中的α-突触核蛋白毒性是由于细胞周期再进入和核糖核苷酸还原酶1的自噬降解引起的
    摘要：α‐Synuclein (aSyn) toxicity is associated with cell cycle alterations, activation of DNA damage responses (DDR), and deregulation of autophagy. However, the relationships between these phenomena remain largely unknown. Here, we demonstrate that in a yeast model of aSyn toxicity and aging, aSyn expression induces Ras2‐dependent growth signaling, cell cycle re‐entry, DDR activation, autophagy, and autophagic degradation of ribonucleotide reductase 1 (Rnr1), a protein required for the activity of ribonucleotide reductase and dNTP synthesis. These events lead to cell death and aging, which are abrogated by deleting RAS2, inhibiting DDR or autophagy, or overexpressing RNR1. aSyn expression in human H4 neuroglioma cells also induces cell cycle re‐entry and S‐phase arrest, autophagy, and degradation of RRM1, the human homologue of RNR1, and inhibiting autophagic degradation of RRM1 rescues cells from cell death. Our findings represent a model for aSyn toxicity that has important implications for understanding synucleinopathies and other age‐related neurodegenerative diseases.
  • 9.

    【2hr】Cell‐type‐specific role of lamin‐B1 in thymus development and its inflammation‐driven reduction in thymus aging

    包量

    机译 Lamin-B1在胸腺发育中的细胞类型特异性作用及其炎症驱动的胸腺衰老减少
    摘要：Cellular architectural proteins often participate in organ development and maintenance. Although functional decay of some of these proteins during aging is known, the cell‐type‐specific developmental role and the cause and consequence of their subsequent decay remain to be established especially in mammals. By studying lamins, the nuclear structural proteins, we demonstrate that lamin‐B1 functions specifically in the thymic epithelial cells (TECs) for proper thymus organogenesis. An up‐regulation of proinflammatory cytokines in the intra‐thymic myeloid immune cells during aging accompanies a gradual reduction of lamin‐B1 in adult TECs. We show that these cytokines can cause senescence and lamin‐B1 reduction of the young adult TECs. Lamin‐B1 supports the expression of TEC genes that can help maintain the adult TEC subtypes we identified by single‐cell RNA‐sequencing, thymic architecture, and function. Thus, structural proteins involved in organ building and maintenance can undergo inflammation‐driven decay which can in turn contribute to age‐associated organ degeneration.
  • 10.

    【2hr】Effects of IGF‐1 isoforms on muscle growth and sarcopenia

    包量

    机译 IGF-1亚型对肌肉生长和肌肉减少症的影响
    摘要：The decline in skeletal muscle mass and strength occurring in aging, referred as sarcopenia, is the result of many factors including an imbalance between protein synthesis and degradation, changes in metabolic/hormonal status, and in circulating levels of inflammatory mediators. Thus, factors that increase muscle mass and promote anabolic pathways might be of therapeutic benefit to counteract sarcopenia. Among these, the insulin‐like growth factor‐1 (IGF‐1) has been implicated in many anabolic pathways in skeletal muscle. IGF‐1 exists in different isoforms that might exert different role in skeletal muscle. Here we study the effects of two full propeptides IGF‐1Ea and IGF‐1Eb in skeletal muscle, with the aim to define whether and through which mechanisms their overexpression impacts muscle aging. We report that only IGF‐1Ea expression promotes a pronounced hypertrophic phenotype in young mice, which is maintained in aged mice. Nevertheless, examination of aged transgenic mice revealed that the local expression of either IGF‐1Ea or IGF‐1Eb transgenes was protective against age‐related loss of muscle mass and force. At molecular level, both isoforms activate the autophagy/lysosome system, normally altered during aging, and increase PGC1‐α expression, modulating mitochondrial function, ROS detoxification, and the basal inflammatory state occurring at old age. Moreover, morphological integrity of neuromuscular junctions was maintained and preserved in both MLC/IGF‐1Ea and MLC/IGF‐1Eb mice during aging. These data suggest that IGF‐1 is a promising therapeutic agent in staving off advancing muscle weakness.
  • 11.

    【2hr】KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke

    包量

    机译 KCNQ1OT1通过调节脑缺血性中风的miR-200a / FOXO3 / ATG7途径促进自噬
    摘要：Dysregulation of long noncoding RNAs (lncRNAs) is associated with abnormal development and pathophysiology in the brain. Increasing evidence has indicated that ischemic stroke is becoming the most common cerebral disease in aging populations. The treatment of ischemic stroke is challenging, due in part to ischemia and reperfusion (I/R) injury. In this study, we revealed that potassium voltage‐gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1) was significantly upregulated in ischemic stroke. Knockdown of KCNQ1OT1 remarkably reduced the infarct volume and neurological impairments in transient middle cerebral artery occlusion (tMCAO) mice. Mechanistically, KCNQ1OT1 acted as a competing endogenous RNA of miR‐200a to regulate downstream forkhead box O3 (FOXO3) expression, which is a transcriptional regulator of ATG7. Knockdown of KCNQ1OT1 might inhibit I/R‐induced autophagy and increase cell viability via the miR‐200a/FOXO3/ATG7 pathway. This finding offers a potential novel strategy for ischemic stroke therapy.
  • 12.

    【2hr】Tendinosis develops from age‐ and oxygen tension‐dependent modulation of Rac1 activity

    包量

    机译 肌腱炎是由年龄和氧气张力对Rac1活性的调节作用发展而来的
    摘要：Age‐related tendon degeneration (tendinosis) is characterized by a phenotypic change in which tenocytes display characteristics of fibrochondrocytes and mineralized fibrochondrocytes. As tendon degeneration has been noted in vivo in areas of decreased tendon vascularity, we hypothesized that hypoxia is responsible for the development of the tendinosis phenotype, and that these effects are more pronounced in aged tenocytes. Hypoxic (1% O2) culture of aged, tendinotic, and young human tenocytes resulted in a mineralized fibrochondrocyte phenotype in aged tenocytes, and a fibrochondrocyte phenotype in young and tendinotic tenocytes. Investigation of the molecular mechanism responsible for this phenotype change revealed that the fibrochondrocyte phenotype in aged tenocytes occurs with decreased Rac1 activity in response to hypoxia. In young hypoxic tenocytes, however, the fibrochondrocyte phenotype occurs with concomitant decreased Rac1 activity coupled with increased RhoA activity. Using pharmacologic and adenoviral manipulation, we confirmed that these hypoxic effects on the tenocyte phenotype are linked directly to the activity of RhoA/Rac1 GTPase in in vitro human cell culture and tendon explants. These results demonstrate that hypoxia drives tenocyte phenotypic changes, and provide a molecular insight into the development of human tendinosis that occurs with aging.
  • 13.

    【2hr】Hyperadrenocorticism of calorie restriction contributes to its anti‐inflammatory action in mice

    包量

    机译 卡路里限制的高肾上腺皮质激素有助于其在小鼠中的抗炎作用
    摘要：Calorie restriction (CR), which lengthens lifespan in many species, is associated with moderate hyperadrenocorticism and attenuated inflammation. Given the anti‐inflammatory action of glucocorticoids, we tested the hypothesis that the hyperadrenocorticism of CR contributes to its attenuated inflammatory response. We used a corticotropin‐releasing‐hormone knockout (CRHKO) mouse, which is glucocorticoid insufficient. There were four controls groups: CRHKO mice and wild‐type (WT) littermates fed either ad libitum (AL) or CR (60% of AL food intake), and three experimental groups: (a) AL‐fed CRHKO mice given corticosterone (CORT) in their drinking water titrated to match the integrated 24‐hr plasma CORT levels of AL‐fed WT mice, (b) CR‐fed CRHKO mice given CORT to match the 24‐hr CORT levels of AL‐fed WT mice, and (c) CR‐fed CHRKO mice given CORT to match the 24‐hr CORT levels of CR‐fed WT mice. Inflammation was measured volumetrically as footpad edema induced by carrageenan injection. As previously observed, CR attenuated footpad edema in WT mice. This attenuation was significantly blocked in CORT‐deficient CR‐fed CRHKO mice. Replacement of CORT in CR‐fed CRHKO mice to the elevated levels observed in CR‐fed WT mice, but not to the levels observed in AL‐fed WT mice, restored the anti‐inflammatory effect of CR. These results indicate that the hyperadrenocorticism of CR contributes to the anti‐inflammatory action of CR, which may in turn contribute to its life‐extending actions.
  • 14.

    【2hr】mTORC1 underlies age‐related muscle fiber damage and loss by inducing oxidative stress and catabolism

    包量

    机译 mTORC1通过诱导氧化应激和分解代谢而成为与年龄相关的肌肉纤维损伤和损失的基础
    摘要：Aging leads to skeletal muscle atrophy (i.e., sarcopenia), and muscle fiber loss is a critical component of this process. The mechanisms underlying these age‐related changes, however, remain unclear. We show here that mTORC1 signaling is activated in a subset of skeletal muscle fibers in aging mouse and human, colocalized with fiber damage. Activation of mTORC1 in TSC1 knockout mouse muscle fibers increases the content of morphologically abnormal mitochondria and causes progressive oxidative stress, fiber damage, and fiber loss over the lifespan. Transcriptomic profiling reveals that mTORC1's activation increases the expression of growth differentiation factors (GDF3, 5, and 15), and of genes involved in mitochondrial oxidative stress and catabolism. We show that increased GDF15 is sufficient to induce oxidative stress and catabolic changes, and that mTORC1 increases the expression of GDF15 via phosphorylation of STAT3. Inhibition of mTORC1 in aging mouse decreases the expression of GDFs and STAT3's phosphorylation in skeletal muscle, reducing oxidative stress and muscle fiber damage and loss. Thus, chronically increased mTORC1 activity contributes to age‐related muscle atrophy, and GDF signaling is a proposed mechanism.
  • 15.

    【2hr】Noncoding variations in Cyp24a1 gene are associated with Klotho‐mediated aging phenotypes in different strains of mice

    包量

    机译 Cyp24a1基因的非编码变异与Klotho介导的不同小鼠品系的衰老表型有关
    摘要：In mutant mice, reduced levels of Klotho promoted high levels of active vitamin D in the serum. Genetic or dietary manipulations that diminished active vitamin D alleviated aging‐related phenotypes caused by Klotho down‐regulation. The hypomorphic Klotho [kl/kl] allele that decreases Klotho expression in C3H, BALB/c, 129, and C57BL/6 genetic backgrounds substantially increases 1,25(OH)2D3 levels in the sera of susceptible C3H, BALB/c, and 129, but not C57BL/6 mice. This may be attributed to increased basal expression of Cyp24a1 in C57BL/6 mice, which promotes inactivation of 1,25(OH)2D3. Decreased expression of Cyp24a1 in susceptible strains was associated with genetic alterations in noncoding regions of Cyp24a1 gene, which were strongly reminiscent of super‐enhancers that regulate gene expression. These observations suggest that higher basal expression of an enzyme required for catabolizing vitamin D renders B6‐kl/kl mice less susceptible to changes in Klotho expression, providing a plausible explanation for the lack of aging phenotypes on C57BL/6 strain.
  • 16.

    【2hr】Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction

    包量

    机译 衰老细胞的药理清除可改善急性心肌梗死后老年小鼠的存活和恢复
    摘要：Cardiovascular disease is the leading cause of death in individuals over 60 years old. Aging is associated with an increased prevalence of coronary artery disease and a poorer prognosis following acute myocardial infarction (MI). With age, senescent cells accumulate in tissues, including the heart, and contribute to age‐related pathologies. However, the role of senescence in recovery following MI has not been investigated. In this study, we demonstrate that treatment of aged mice with the senolytic drug, navitoclax, eliminates senescent cardiomyocytes and attenuates profibrotic protein expression in aged mice. Importantly, clearance of senescent cells improved myocardial remodelling and diastolic function as well as overall survival following MI. These data provide proof‐of‐concept evidence that senescent cells are major contributors to impaired function and increased mortality following MI and that senolytics are a potential new therapeutic avenue for MI.
  • 17.

    【2hr】Long‐term caloric restriction ameliorates deleterious effects of aging on white and brown adipose tissue plasticity

    包量

    机译 长期热量限制可改善衰老对白色和棕色脂肪组织可塑性的有害影响
    摘要：Age‐related increased adiposity is an important contributory factor in the development of insulin resistance (IR) and is associated with metabolic defects. Caloric restriction (CR) is known to induce weight loss and to decrease adiposity while preventing metabolic risk factors. Here, we show that moderate 20% CR delays early deleterious effects of aging on white and brown adipose tissue (WAT and BAT, respectively) function and improves peripheral IR. To elucidate the role of CR in delaying early signs of aging, young (3 months), middle‐aged (12 months), and old (20 months) mice fed al libitum and middle‐aged and old mice subjected to early‐onset CR were used. We show that impaired plasticity of subcutaneous WAT (scWAT) contributes to IR, which is already evident in middle‐aged mice. Moreover, alteration of thyroid axis status with age is an important factor contributing to BAT dysfunction in middle‐aged animals. Both defects in WAT and BAT/beige cells are ameliorated by CR. Accordingly, CR attenuated the age‐related decline in scWAT function and decreased the extent of fibro‐inflammation. Furthermore, CR promoted scWAT browning. In brief, our study identifies the contribution of scWAT impairment to age‐associated metabolic dysfunction and identifies browning in response to food restriction, as a potential therapeutic strategy to prevent the adverse metabolic effects in middle‐aged animals.
  • 18.

    【2hr】Glycine supplementation extends lifespan of male and female mice

    包量

    机译 补充甘氨酸可延长雄性和雌性小鼠的寿命
    摘要：Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%–6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p < 0.001). Pooling across sex, glycine increased lifespan at each of the three independent sites, with significance at p = 0.01, 0.053, and 0.03, respectively. Glycine‐supplemented females were lighter than controls, but there was no effect on weight in males. End‐of‐life necropsies suggested that glycine‐treated mice were less likely than controls to die of pulmonary adenocarcinoma (p = 0.03). Of the 40 varieties of incidental pathology evaluated in these mice, none were increased to a significant degree by the glycine‐supplemented diet. In parallel analyses of the same cohort, we found no benefits from TM5441 (an inhibitor of PAI‐1, the primary inhibitor of tissue and urokinase plasminogen activators), inulin (a source of soluble fiber), or aspirin at either of two doses. Our glycine results strengthen the idea that modulation of dietary amino acid levels can increase healthy lifespan in mice, and provide a foundation for further investigation of dietary effects on aging and late‐life diseases.
  • 19.

    【2hr】IL‐1α cleavage by inflammatory caspases of the noncanonical inflammasome controls the senescence‐associated secretory phenotype

    包量

    机译 IL-1α被非规范性炎症小体的炎性胱天蛋白酶裂解控制了与衰老相关的分泌表型
    摘要：Interleukin‐1 alpha (IL‐1α) is a powerful cytokine that modulates immunity, and requires canonical cleavage by calpain for full activity. Mature IL‐1α is produced after inflammasome activation and during cell senescence, but the protease cleaving IL‐1α in these contexts is unknown. We show IL‐1α is activated by caspase‐5 or caspase‐11 cleavage at a conserved site. Caspase‐5 drives cleaved IL‐1α release after human macrophage inflammasome activation, while IL‐1α secretion from murine macrophages only requires caspase‐11, with IL‐1β release needing caspase‐11 and caspase‐1. Importantly, senescent human cells require caspase‐5 for the IL‐1α‐dependent senescence‐associated secretory phenotype (SASP) in vitro, while senescent mouse hepatocytes need caspase‐11 for the SASP‐driven immune surveillance of senescent cells in vivo. Together, we identify IL‐1α as a novel substrate of noncanonical inflammatory caspases and finally provide a mechanism for how IL‐1α is activated during senescence. Thus, targeting caspase‐5 may reduce inflammation and limit the deleterious effects of accumulated senescent cells during disease and Aging.
  • 20.

    【2hr】NAD+ supplementation rejuvenates aged gut adult stem cells

    包量

    机译 NAD +补充剂可以使衰老的肠道成年干细胞恢复活力
    摘要：The tissue decline due to aging is associated with the deterioration of adult stem cell function. Here we show the number and proliferative activity of intestinal stem cells (ISCs) but not Paneth cells decline during aging, as does ISC function assessed ex vivo. Levels of SIRT1 and activity of mTORC1 also decline with aging. The treatment with the NAD(+) precursor nicotinamide riboside (NR) rejuvenates ISCs from aged mice and reverses an impaired ability to repair gut damage. The effect of NR is blocked by the mTORC1 inhibitor rapamycin or the SIRT1 inhibitor EX527. These findings demonstrate that small molecules affecting the NAD/SIRT1/mTORC1 axis may guide a translational path for maintenance of the intestine during aging.
题名 作者 来源 发表时间

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号