Gene expression profile of the aging process in rat liver: normalizing effects of growth hormone replacement.
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.
Tollet-Egnell
P
P
Department of Molecular Medicine, Karolinska Institutet, CMM L8:01, Karolinska Hospital, 171 76 Stockholm, Sweden. petra.tollet.egnell@molmed.ki.se
Flores-Morales
A
A
Ståhlberg
N
N
Malek
R L
RL
Lee
N
N
Norstedt
G
G
D000375:Aging / Q000235:genetics*; D000818:Animals; D018076:DNA, Complementary / Q000032:analysis / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D020249:Hormone Replacement Therapy; D008099:Liver / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D004364:Pharmaceutical Preparations / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D018076:DNA, Complementary; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D013006:Growth Hormone