The long-term objective of the proposed research is to develop an appropriate methodology and test the hypothesis that the heterogeneity of aging is reflected and can be studied at the level of expression profiles of aging tissues. We believe that, on the long term, this approach will help in the systematic deciphering of the multiple basic mechanisms of aging. The main obstacle of a study of the heterogeneity of aging on the level of expression profiling is the high cost, especially because many samples have to be processed. Consequently, the methodological portion of the proposal seeks to develop a low cost, custom array methodology based on membrane immobilized long oligonucleotide probes. We propose to test this methodology on two well-defined biological systems including aging/transgenic heart and cellular replicative senescence. We propose to further use this methodology to accumulate date necessary to test the heterogeneity hypothesis.
| Bodyak, Natalya; Kang, Peter M; Hiromura, Makoto et al. (2002) Gene expression profiling of the aging mouse cardiac myocytes. Nucleic Acids Res 30:3788-94 |
| Coller, Hilary A; Bodyak, Natalya D; Khrapko, Konstantin (2002) Frequent intracellular clonal expansions of somatic mtDNA mutations: significance and mechanisms. Ann N Y Acad Sci 959:434-47 |
| Coller, H A; Khrapko, K; Bodyak, N D et al. (2001) High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection. Nat Genet 28:147-50 |
