Department of Pathology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania.
Ann N Y Acad Sci. 2018 Apr;1418(1):95-105. doi: 10.1111/nyas.13566. Epub 2018 Jan 28.
Both methionine restriction and rapamycin treatment are robust longevity-enhancing regimens for which the mechanisms remain unclear. Cellular senescence is a major contributor to the aging process, and we find that both the methionine and rapamycin regimens delay or prevent activation of the senescence program in human cells. Using a transcriptome-wide analysis, we examined the impact of methionine restriction and rapamycin treatment on senescence-associated gene expression in human cardiac fibroblasts. Our findings have been integrated into gene expression data sets from human lung and skin fibroblasts during senescence. The data demonstrate both common and tissue-specific aspects to the senescent phenotype in these cell types. For example, cardiac fibroblasts express brain naturetic peptide, a clinically relevant marker for cardiac failure, whereas senescent cells from all three tissues express at least one of the insulin-like growth factor (IGF)-binding proteins. The IGF-binding proteins are tissue-specific mediators of IGF-1, a growth factor required for proliferation of all tissues. These data suggest that senescent cells serve tissue-specific roles. Moreover, the prolongevity regimens produce distinct patterns of gene expression.
甲硫氨酸限制和雷帕霉素治疗都是强有力的延长寿命的方案，但它们的机制尚不清楚。细胞衰老（cellular senescence）是衰老过程的一个主要贡献者，我们发现，甲硫氨酸和雷帕霉素方案都可以延迟或预防人类细胞中衰老程序的激活。我们使用全转录组分析，研究了甲硫氨酸限制和雷帕霉素治疗对人类心脏成纤维细胞衰老相关基因表达的影响。我们的研究结果已经整合到人类肺和皮肤成纤维细胞衰老过程中的基因表达数据集。这些数据表明，在这些细胞类型中，衰老表型既有共同的又有组织特异性的方面。例如，心脏成纤维细胞表达脑钠肽（natriuretic peptide），这是心力衰竭的一个临床相关标志物，而所有三种组织的衰老细胞都至少表达一种胰岛素样生长因子（IGF）结合蛋白。IGF 结合蛋白是 IGF-1 的组织特异性介质，IGF-1 是所有组织增殖所必需的生长因子。这些数据表明衰老细胞发挥组织特异性作用。此外，长寿方案产生了不同的基因表达模式。
