Senescence-Related Changes in Gene Expression of Peripheral Blood Mononuclear Cells from Octo/Nonagenarians Compared to Their Offspring
Senescence-Related Changes in Gene Expression of Peripheral Blood Mononuclear Cells from Octo/Nonagenarians Compared to Their Offspring
复制标题
DOI：
10.1155/2013/189129
复制
发表时间：
2013-01-01
影响因子：
--
通讯作者：
Ngah, Wan Zurinah Wan
中科院分区：
文献类型：
--
作者：
Rahman, Amirah Abdul;Karim, Norwahidah Abdul;Ngah, Wan Zurinah Wan
在衰老过程中，决定功能衰退速度和发病时间的机制仍然难以捉摸。对衰老过程的研究，特别是那些涉及到长寿个体和年轻对照的比较的研究是相当有限的。因此，本研究旨在确定马来西亚彭亨村相关个体的差异基因表达谱。对80-99岁高龄老人及其后代（50.2 +/- 4.0岁）18份外周血单核细胞（PBMCs）样本的全基因组微阵列分析显示，与后代相比，80-99岁高龄老人的477份转录本是年龄诱导的，335份转录本是年龄抑制的，其倍数变化>= 1.2。有趣的是，基因表达的变化与凋亡（BAK1）、细胞周期调节（CDKN1B）、代谢过程（LRPAP1）、胰岛素作用（IGF2R）以及免疫和炎症反应（IL27RA）的增加有关，而对应激（HSPA8）、损伤刺激（XRCC6）和染色质重塑（TINF2）途径的反应在10岁/ 90岁老人中下调。这些结果表明，随着年龄的增长，系统端粒维持、代谢、细胞信号传导和氧化还原调节可能对个体保持健康状态很重要，这些过程在健康寿命的决定中起着重要作用。
Mechanisms determining both functional rate of decline and the time of onset in aging remain elusive. Studies of the aging process especially those involving the comparison of long-lived individuals and young controls are fairly limited. Therefore, this research aims to determine the differential gene expression profile in related individuals from villages in Pahang, Malaysia. Genome-wide microarray analysis of 18 samples of peripheral blood mononuclear cells (PBMCs) from two groups: octo/nonagenarians (80-99 years old) and their offspring (50.2 +/- 4.0 years old) revealed that 477 transcripts were age-induced and 335 transcripts were age-repressed with fold changes >= 1.2 in octo/nonagenarians compared to offspring. Interestingly, changes in gene expression were associated with increased capacity for apoptosis (BAK1), cell cycle regulation (CDKN1B), metabolic process (LRPAP1), insulin action (IGF2R), and increased immune and inflammatory response (IL27RA), whereas response to stress (HSPA8), damage stimulus (XRCC6), and chromatin remodelling (TINF2) pathways were downregulated in octo/nonagenarians. These results suggested that systemic telomere maintenance, metabolism, cell signalling, and redox regulation may be important for individuals to maintain their healthy state with advancing age and that these processes play an important role in the determination of the healthy life-span.