Four years ago in Science, Stuart Kim, a Stanford University developmental biologist, made the case for describing the broad strokes of a complex physiological process before defining its mechanisms. "A powerful, top-down, holistic approach," he wrote, "is to identify all of the components of a particular cellular process, so that one can define the global picture first and then use it as a framework to understand how the individual components of the process fit together." To get a broad view of gene expression in the developing nematode, Kims lab turned to DNA microarray technology. In a new study, Kim and colleagues apply this same approach to the decidedly more complex problem of human aging and "present a molecular portrait" of the aging kidney.
Genome-wide analysis of aging in the human kidney. Photo illustration by Rebecca Sonu and Emily Crane.
Kidneys came from 74 patients, ranging in age from 27 to 92. Samples were extracted from donated kidneys or "meticulously harvested" from kidneys with localized disease to ensure only normal tissue was taken. Samples were obtained from two structures that are critical to kidney function: the renal cortex, which filters plasma, and the medulla, which alters urine composition to maintain fluid balance. Both deteriorate with age.
Kim and colleagues then used DNA microarrays to determine the activity of every gene in all the kidney samples. Of 33,000 known human genes on the microarray, 985 showed age-related changes.
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