Life spanning murine gene expression profiles in relation to chronological and pathological aging in multiple organs.
Life spanning murine gene expression profiles in relation to chronological and pathological aging in multiple organs.
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DOI：
10.1111/acel.12118
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发表时间：
2013-10
期刊：
影响因子：
7.8
通讯作者：
van Steeg H
中科院分区：
文献类型：
--
作者：
Jonker MJ;Melis JP;Kuiper RV;van der Hoeven TV;Wackers PFK;Robinson J;van der Horst GT;Dollé ME;Vijg J;Breit TM;Hoeijmakers JH;van Steeg H
衰老和与年龄相关的病理是一个仍未完全理解的分子和细胞过程的复杂网络的结果。我们对C57BL/6J雌性小鼠的五个器官（肝、肾、脾、肺和脑）进行了体内衰老研究，在该研究中，我们比较了小鼠整个生命周期（13、26、52、78、104和130周）中按时间顺序衰老的全基因组基因表达谱和病理变化。将基因表达变化与时间衰老联系起来表明，在大多数器官中发现了许多差异表达基因（deg）和改变的基因集（AGSs），表明器官内的一般衰老过程。然而，在所有器官中发现的这些deg仅占≤1%。对于每个器官，18个测试病理参数中至少有一个显示出良好的年龄预测价值，尽管个体间和个体内（器官）差异很大。将基因表达变化与病理相关衰老联系起来，揭示了相关的基因和基因集，从而使生物学衰老和实年性衰老的差异得以表征。在肝、肾和脑中，发现了数量有限的重叠病理相关的AGSs。免疫反应似乎很常见，但这种变化在大多数器官中都是特异性的。此外，还观察到能量稳态、活性氧、细胞周期、细胞运动和DNA损伤的变化。时间和病理相关AGSs的比较显示了大量的重叠和有趣的差异。例如，在肝脏病理相关的AGSs中存在免疫过程，而这些过程在时间衰老中未被检测到。许多细胞过程，只有发现利用衰老相关的病理学可以提供重要的新见解的进展衰老。
Aging and age-related pathology is a result of a still incompletely-understood intricate web of molecular and cellular processes. We present a C57BL/6J female mice in vivo aging study of five organs (liver, kidney, spleen, lung and brain), in which we compare genome-wide gene expression profiles during chronological aging with pathological changes throughout the entire murine lifespan (13, 26, 52, 78, 104 and 130 weeks). Relating gene expression changes to chronological aging revealed many differentially expressed genes (DEGs) and altered gene-sets (AGSs) were found in most organs, indicative of intra-organ generic aging processes. However, only ≤ 1% of these DEGs are found in all organs. For each organ, at least one of 18 tested pathological parameters showed a good age-predictive value, albeit with much inter- and intra-individual (organ) variation. Relating gene expression changes to pathology-related aging revealed correlated genes and gene-sets, which made it possible to characterize the difference between biological and chronological aging. In liver, kidney and brain, a limited number of overlapping pathology-related AGSs were found. Immune responses appeared to be common, yet the changes were specific in most organs. Furthermore, changes were observed in energy homeostasis, reactive oxygen species, cell cycle, cell motility and DNA damage. Comparison of chronological and pathology-related AGSs revealed substantial overlap and interesting differences. For example, the presence of immune processes in liver pathology-related AGSs which were not detected in chronological aging. The many cellular processes that are only found employing aging–related pathology could provide important new insights into the progress of aging.
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影响因子：
7.8
作者：
Park SK;Kim K;Page GP;Allison DB;Weindruch R;Prolla TA
通讯作者：
Prolla TA
DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D
影响因子：
1.5
作者：
Haines, DC;Chattopadhyay, S;Ward, JM
通讯作者：
Ward, JM
影响因子：
1.8
作者：
de Leeuw, Wim C;Rauwerda, Han;Jonker, Martijs J;Breit, Timo M
通讯作者：
Breit, Timo M
影响因子：
30.8
作者：
Parkes, TL;Elia, AJ;Boulianne, GL
通讯作者：
Boulianne, GL