CHANGES IN GENE EXPRESSION IN SENESCENT MUSCLE

University Of Rochester, Rochester NY

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Abstract

Preliminary studies have identified numerous mRNAs that may be under- or over-expressed in senescent human muscle relative to young adult muscle. The objective of the proposed research is to prospectively determine which of these transcripts are consistently affected by aging, and to further characterize these differences. Specifically, the relation between mRNA expression and protein expression will be examined in human muscle samples obtained from younger (18-29 yr) and older (65-79 yr) men and women. Because type 2 muscle fibers tend to atrophy more with age than type 1 fibers, the relative expression of these mRNAs in different fiber types will be determined. Many of the transcripts under-expressed in older muscle in the preliminary study encode mitochondrial proteins involved in electron transport and ATP synthesis. The roles of mitochondrial DNA copy number, mitochondrial transcription factor A, and nuclear respiratory factors in the under-expression of these mRNAs will be examined. Many of the transcripts differentially expressed in the preliminary study have been only partially sequenced. For those that are also differentially expressed in the prospective study, the full mRNA sequence will be determined. This information will be used to deduce the amino acid sequence, allowing studies of protein expression, and possibly providing clues about protein function. The knowledge generated by the proposed research may lead to a better understanding of the molecular basis of muscle atrophy and dysfunction in old age, and a better understanding of the basic biology of aging of postmitotic cells.