Searching for genetic determinants of human aging and longevity: opportunities and challenges

One way of testing possible causal relationships between various functional pathways and aging and longevity processes is to comparatively analyze groups of elderly individuals with select phenotypes for sequence variation in all genes participating in these pathways. Such direct association analysis to identify 'candidate pathways' in aging and longevity is theoretically feasible, with the complete sequence of the human genome known and massive gene annotation projects underway. To find all possible sequence variation of a large number of genes in aging populations, efficient genotyping methods are needed. Here, we describe the use of one such method, two-dimensional gene scanning (TDGS), for screening populations of centenarians and controls for polymorphic variation in the large BRCA1 breast cancer susceptibility gene.