Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice
Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice
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DOI：
10.1073/pnas.191313598
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发表时间：
2001-09-11
影响因子：
11.1
通讯作者：
Spindler, SR
中科院分区：
文献类型：
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作者：
Cao, SX;Dhahbi, JM;Spindler, SR
我们对衰老的潜在有丝分裂组织肝脏中的11，000个基因进行了全基因组微阵列表达分析。这个器官对衰老过程中的健康和体内平衡有重大影响。研究了延长寿命和健康寿命的热量限制（CR）对年轻和老年小鼠以及长期CIR（LT-CR）和短期CR（ST-CR）之间基因表达的影响。这种实验设计使我们能够准确地区分衰老对基因表达的影响和CR对基因表达的影响。衰老伴随着与炎症增加、细胞应激和纤维化相关的基因表达的变化，以及细胞凋亡、异生物质代谢、正常细胞周期和DNA复制能力的降低。LT-CR和仅4周的ST-CR逆转了大多数这些变化。LT-CR在年轻小鼠中产生的基因表达模式是在老年LT-CR小鼠中发现的变化的子集。基因表达的早期变化（持续到老年）可能是CR延长寿命和健康寿命的关键。此外，ST-CR基本上将老年对照小鼠的“正常老化”基因组谱向与LT-CR相关的“缓慢老化”谱转移。因此，CR的许多基因组效应迅速建立。因此，表达谱应证明在快速鉴定CR模拟药物和治疗中是有用的。
We present genome-wide microarray expression analysis of 11,000 genes in an aging potentially mitotic tissue, the liver. This organ has a major impact on health and homeostasis during aging. The effects of life- and health-span-extending caloric restriction (CR) on gene expression among young and old mice and between long-term CIR (LT-CR) and short-term CR (ST-CR) were examined. This experimental design allowed us to accurately distinguish the effects of aging from those of CR on gene expression. Aging was accompanied by changes in gene expression associated with increased inflammation, cellular stress, and fibrosis, and reduced capacity for apoptosis, xenobiotic metabolism, normal cell-cycling, and DNA replication. LT-CR and just 4 weeks of ST-CR reversed the majority of these changes. LT-CR produced in young mice a pattern of gene expression that is a subset of the changes found in old LT-CR mice. It is possible that the early changes in gene expression, which extend into old age, are key to the life- and health-span-extending effects of CR. Further, ST-CR substantially shifted the "normo-aging" genomic profile of old control mice toward the "slow-aging" profile associated with LT-CR. Therefore, many of the genomic effects of CR are established rapidly. Thus, expression profiling should prove useful in quickly identifying CR-mimetic drugs and treatments.