Gene Expression Profile of the Aging Process in Rat Liver: Normalizing Effects of Growth Hormone Replacement

Abstract

The mechanisms that control life span and age-related phenotypes are not well understood. It has been suggested that aging or at least some of its symptoms are related to a physiological decline in GH levels with age. To test this hypothesis, and to improve our understanding of the cellular and molecular mechanisms behind the aging process, we have analyzed age-induced changes in gene expression patterns through the application of DNA chip technology. In the present study, the aging process was analyzed in rat liver in the presence or absence of GH replacement. Out of 3,000 genes printed on the microarrays, approximately 1,000 were detected in the rat liver. Among these, 47 unique transcripts were affected by the aging process in male rat livers. The largest groups of age-regulated transcripts encoded proteins involved in intermediary metabolism, mitochondrial respiration, and drug metabolism. Approximately 40% of the differentially expressed gene products were normalized after GH treatment. The majority of those transcripts have previously not been shown to be under GH control. The list of gene products that showed normalized expression levels in GH-treated old rats may shed further insight on the action and mechanism behind the positive effects of GH on, for example, fuel metabolism and body composition observed in different animal and human studies.

A large-scale screening of the normalized mammalian mitochondrial gene expression profiles

“…Total mitochondrial gene expression seems to be a direct function of ageing, and generally declines with age, as has been demonstrated in a number of studies (Bodyak et al, 2002 ;Lu et al, 2004), while the activity of mitochondrial enzymes is suggested as a biochemical marker of ageing (Navarro et al, 2004). Importantly, ageing might affect the expression of individual mitochondrial genes to various extents (Tollet-Egnell et al, 2001). Quantitatively accurate data from both publicly available ageing-related SAGE studies (Welle et al, 2000 ;Anisimov et al, 2005) provide a degree of support for this hypothesis.…”

Pre‐mRNA splicing modulations in senescence

“…This involves the expression levels of a large number of transcription factors, also shown to be modified in aged tissues Cao et al ., 2001;Tollet-Egnell et al ., 2001). Since transcription and splicing are tightly coupled (Schwer & Gross, 1998) *From Lee et al (1999).…”

“…For example, these may all reflect one or a few changes in regulatory factor(s), such as splicing-related proteins, which modify the delicate regulation of the splicing process. Support for this concept can be found in recent microarray screens for changes in gene expression during aging Shelton et al ., 1999;Cao et al ., 2001;Tollet-Egnell et al ., 2001). Significant age-related tissuespecific changes were found in the expression levels of several RNA processing genes in aged, compared to young, gastrocnemius muscle, neocortex and cerebellum of C57BL /6 mice .…”

Exploration of replicative senescence-associated genes in human dermal fibroblasts by cDNA microarray technology

“…RNA differential displays and the serial assessment of gene expression (Welle et al, 2001) have been applied to explore senescence-associated genes to gain an insight into the molecular mechanisms underlying senescence. Moreover, recent advances in cDNA array technology have made it possible to analyze global gene expressions, and a variety of genes involved in cell cycle regulation, immune and inflammation, cytoskeleton, stress response, and metabolism are known to be altered during cellular senescence (Shelton et al, 1999;Ly et al, 2000;Zhang et al, 2003) and animal models (Lee et al, 1999(Lee et al, , 2000Tollet-Egnell et al, 2001;Kayo et al, 2001;Cao et al, 2001). Shelton et al (1999) assessed senescence-associated gene expression in dermal fibroblasts using a 1 k cDNA microarray and concluded that the senescent state mimics inflammatory wound repair processes.…”