Abstract
BackgroundThe aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on ad libitum (AL) feeding with a group on lifespan-extending 40% calorie restriction (CR).ResultsWe found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months), whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis.ConclusionOverall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary.
Highlights
The aging of reproductive organs is a major social issue, but of special interest in aging research
Experimental design We analyzed gene expression patterns in ovaries and testes sampled from 1, 6, 16, and 24-month-old C57BL/6 mice fed on ad libitum (AL) and calorie restriction (CR) diets (Figure 1A and 1D)
Mice were kept on an AL diet until 14 weeks of age and split into AL and CR gonads [20]
Summary
The aging of reproductive organs is a major social issue, but of special interest in aging research. Global gene expression profiling is beginning to provide molecular signatures of aging in various organs and tissues [1,2]. Aged muscles show a reduced expression of genes involved in energy metabolism and an increased expression of heat-shock proteins and oxidative-stress inducible genes [3]. Aged brain tissues show increased expression of genes associated with stress and the inflammatory response and decreased expression of genes associated with the ubiquitin-proteasome pathway and growth factors [2,4]. Global gene expression profiling has revealed that age-related gene expression changes in muscle are completely [5] or partially [6] suppressed by calorie restriction (CR), which is a factor capable of increasing the lifespan in organisms, including rodents [7,8,9]. It has been shown that age-related decrease in the induction of Hsp in response to heat stress in rat hepatocytes is partially reversed by CR [10]
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