Transcriptional Profiling of Aging in Human Muscle Reveals a Common Aging Signature

Abstract

We analyzed expression of 81 normal muscle samples from humans of varying ages, and have identified a molecular profile for aging consisting of 250 age-regulated genes. This molecular profile correlates not only with chronological age but also with a measure of physiological age. We compared the transcriptional profile of muscle aging to previous transcriptional profiles of aging in the kidney and the brain, and found a common signature for aging in these diverse human tissues. The common aging signature consists of six genetic pathways; four pathways increase expression with age (genes in the extracellular matrix, genes involved in cell growth, genes encoding factors involved in complement activation, and genes encoding components of the cytosolic ribosome), while two pathways decrease expression with age (genes involved in chloride transport and genes encoding subunits of the mitochondrial electron transport chain). We also compared transcriptional profiles of aging in humans to those of the mouse and fly, and found that the electron transport chain pathway decreases expression with age in all three organisms, suggesting that this may be a public marker for aging across species.

Synopsis

Aging is a complex phenomenon characterized by the decay of biological function over time, eventually leading to death. High-throughput methods for examining changes in the expression of genes, such as DNA microarrays, have been successful in elucidating some of the genome-wide changes that occur with age in several human tissues. The authors profiled gene expression changes in the muscles of 81 individuals with ages spanning eight decades. They found 250 genes and 3 genetic pathways that displayed altered levels of expression in the elderly. The transcriptional profile of age-regulated genes was able to discern elderly patients with severe muscle aging from those that retained high levels of muscle function; that is, the gene expression profiles reflected physiological as well as chronological age. In order to find genetic changes that might affect most or all tissues during aging, the authors compared genome-wide profiles of aging in the muscle to those in the kidney and the brain, and found a common signature for aging shared among these three tissues consisting of six genetic pathways. One of these aging pathways (the electron transport chain pathway) is age regulated not only in humans but also in two model organisms (mice and flies), providing insights about shared age-related changes in animals with vastly different lifespans.