Gene expression profiling of Healthy Centenarians

Laboratory of Molecular Oncology, INRCA, Ancona, Italy; ITBM, CNR, Rome, Italy; Univ. of Bologna; Dept. of Neurology and Psychiatrics, Univ. of Firenze, Italy; Dept. of Laboratory Medicine and Pathobiology, and Laboratory of Molecular Pathology, Sunnybrook and Women’s College Health Sciences Center, Univ. of Toronto, ON Canada * Corresponding author. INTRODUCTION. Human aging is characterized by a complex remodeling of immune, endocrine, metabolic parameters. In particular, organismal aging is characterized by high levels of proinflammatory molecules paralleling a progressive decay of response to stress at cellular and systemic level The few data on centenarian fibroblasts suggest that these cells possess only some features of replicative senescence, indicating that in vitro senescence plays a role, but do not fully mimic in vivo senescence. On the whole, aging is more appropriately to be considered as the consequence of the remodeling of an expression pattern involving a great number of genes. To compare the pattern of gene expression in centenarians vs. young control fibroblasts, an array of 384 genes was designed and cDNAs were robotically spotted. Genes were chosen on the basis of relationship with cell senescence, role in cellular stress response, involvement in apoptosis, genes involved in inflammation, tumor suppressor genes, cell cycle regulators, genes whose products have been demonstrated to change during aging, and genes whose genetic variants have been associated with human longevity.