Applications Of Microarrays To Human Aging

The application of microarrays to study aging-related processes in humans is, for obvious reasons, more difficult than in model organisms. Availability of samples from healthy donors, genetic and environmental heterogeneity, and variation in sample quality and preparation are just a few of the possible confounding issues. Of particular concern in samples obtained from elderly people is the possibility that medications or other interventions prescribed for a variety of age-associated ailments might alter the normal gene expression profile.

Many studies have reported changes in gene expression as a function of age in humans, and age-correlated gene expression profiles have been described for several tissue types, including retina (Yoshida et al., 2002), muscle (Welle et al., 2004; Welle et al., 2003), kidney (Rodwell et al., 2004), and brain (Lu et al., 2004). Microarrays have also been used to examine gene expression profiles of human cells cultured in vitro. This approach has the benefit of being more controlled and less resource limited than assaying expression in tissues directly from donors, but is subject to a host of caveats associated with the process of obtaining and maintaining stable cell lines in vitro. In addition, the relevance of in vitro replicative senescence to in vivo cellular aging has yet to be determined.

In vitro gene expression profiles have been generated for two progeroid syndromes, Werner syndrome (Kyng et al., 2003) and Hutchinson-Guilford progeria syndrome (Csoka et al., 2004). It has been suggested that most of the changes in gene expression associated with normal aging are recapitulated in cell lines derived from Werner syndrome patients (Kyng et al., 2003), although methodological problems make this interpretation questionable (Prolla, 2005). Interestingly, the gene expression changes observed in fibroblasts from Hutchinson-Guilford progeria syndrome patients show almost no similarity to gene expression changes observed in fibro-blasts from aged donors, nor do they correspond to age-related changes in tissues from mice (Prolla, 2005).

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