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Changes in gene expression associated with aging commonly originate during juvenile growth.

ABSTRACT: In mammals, proliferation is rapid in many tissues during early postnatal life, causing rapid somatic growth. This robust proliferation is then suppressed as the animal approaches adult size, bringing many tissues to a quiescent state where proliferation occurs only as needed to replace dying cells. Recent evidence suggests that the mechanism responsible for this decline in proliferation involves a multi-organ genetic program. We hypothesized that this genetic program continues to progress into later adult life, eventually suppressing proliferation to levels below those needed for tissue renewal, thus contributing to aging. We therefore used expression microarray to compare the temporal changes in gene expression that occur in adult mouse organs during aging to those occurring as juvenile proliferation slows. We found that many of the changes in gene expression that occur during the aging process originate during the period of juvenile growth deceleration. Bioinformatic analyses of the genes that show persistent decline in expression throughout postnatal life indicated that cell-cycle-related genes are strongly over-represented. Thus, the findings support the hypothesis that the genetic program that slows juvenile growth to limit body size persists into adulthood and thus may eventually hamper tissue maintenance and repair, contributing to the aging process.

SUBMITTER: Lui JC

PROVIDER: S-EPMC2956763 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Changes in gene expression associated with aging commonly originate during juvenile growth.

Lui Julian C JC Chen Weiping W Barnes Kevin M KM Baron Jeffrey J

Mechanisms of ageing and development 20100909 10

In mammals, proliferation is rapid in many tissues during early postnatal life, causing rapid somatic growth. This robust proliferation is then suppressed as the animal approaches adult size, bringing many tissues to a quiescent state where proliferation occurs only as needed to replace dying cells. Recent evidence suggests that the mechanism responsible for this decline in proliferation involves a multi-organ genetic program. We hypothesized that this genetic program continues to progress into ...[more]

PMID: 20816690

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Project description:BackgroundAlthough high-throughput studies of gene expression have generated large amounts of data, most of which is freely available in public archives, the use of this valuable resource is limited by computational complications and non-homogenous annotation. To address these issues, we have performed a complete re-annotation of public microarray data from human skeletal muscle biopsies and constructed a muscle expression compendium consisting of nearly 3000 samples. The created muscle compendium is a publicly available resource including all curated annotation. Using this data set, we aimed to elucidate the molecular mechanism of muscle aging and to describe how physical exercise may alleviate negative physiological effects.ResultsWe find 957 genes to be significantly associated with aging (p < 0.05, FDR = 5 %, n = 361). Aging was associated with perturbation of many central metabolic pathways like mitochondrial function including reduced expression of genes in the ATP synthase, NADH dehydrogenase, cytochrome C reductase and oxidase complexes, as well as in glucose and pyruvate processing. Among the genes with the strongest association with aging were H3 histone, family 3B (H3F3B, p = 3.4 × 10(-13)), AHNAK nucleoprotein, desmoyokin (AHNAK, p = 6.9 × 10(-12)), and histone deacetylase 4 (HDAC4, p = 4.0 × 10(-9)). We also discover genes previously not linked to muscle aging and metabolism, such as fasciculation and elongation protein zeta 2 (FEZ2, p = 2.8 × 10(-8)). Out of the 957 genes associated with aging, 21 (p < 0.001, false discovery rate = 5 %, n = 116) were also associated with maximal oxygen consumption (VO2MAX). Strikingly, 20 out of those 21 genes are regulated in opposite direction when comparing increasing age with increasing VO2MAX.ConclusionsThese results support that mitochondrial dysfunction is a major age-related factor and also highlight the beneficial effects of maintaining a high physical capacity for prevention of age-related sarcopenia.

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Changes in gene expression associated with aging commonly originate during juvenile growth.

Publications

Changes in gene expression associated with aging commonly originate during juvenile growth.

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