A research report published in Plos One (open source - you can read it) finds that 6 months of resistance training exercise changes gene expression patterns in aged muscle to look more like youthful muscle.
Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training.
The reversal isn't complete. Aged muscles are still weaker and their gene expression patterns are still different than youthful patterns.
We need to know why the aged muscles do not fully regain youthful strength when exercised. Perhaps losses of muscle cells through cell death leaves too few muscle cells to regain youthful strength. Or maybe limitations in aged vasculature prevents enough oxygen and nutrients from getting through.
The resistance training exercise does not simply substitute for a lower level of exercise in the elderly. Younger control subjects who did not exercise much had youthful gene expression profiles even though they didn't exercise much.
It is possible that our observation of a reversal of the mitochondrial based aging signatures could indicate that the response to exercise training was solely due to lower habitual exercise in the older adults. Arguing against this is the fact that the current study was specifically designed to avoid this confounder by selecting healthy, active, disease-free older adults and comparing them to similarly active younger adults (relatively inactive for age). In the future, it will be important to determine whether long-term or life-long exercise in humans can attenuate the transcriptome signature of aging using cross-sectional sampling in Masters athletes.
We need a gene therapy delivery mechanism that can deliver replacement mitochondrial DNA (mtDNA) into muscle tissues. Such a therapy would help us answer the question of whether accumulated mtDNA damage is a substantial cause of muscle aging. I hope the answer is "yes" because methods to replace mtDNA will be much easier to develop than methods to replace nuclear DNA (i.e. the DNA in chromosomes in the nucleus of cells). Why the difference in difficulty? The nucleus contains over 2.9 billion base pairs of DNA whereas the mtDNA contains about 15,000 base pairs. So development of methods to deliver replacement mtDNA should be a relatively simpler task.
|Share |||Randall Parker, 2007 May 28 10:43 PM Aging Exercise Studies|