Virtually nothing is known about the retrotransposal portion of human genome during aging. Their epigenetic makeup is poorly understood and poorly annotated at the genomic level, due to their high degree of sequence conservation. However, clear evidence exists that during mammalian evolution a large number of ancient retro-elements acquired regulatory or structural functions. While it is known that mis-regulation of retrotransposal portion of the genome impact on the genome stability, the role of aberrant retrotransposal transcription during aging have not yet been fully elucidated. Recent evidence, however indicates that disregulation of retrotransposal RNA processing is associated with diseases such as cancer, macular degeneration, autoimmunity as well as with human adult stem cell aging ex-vivo. This proposal is designed to interrogate age-related differences in aging-epigenome-retrotransposon relationship by using power of innovative next generation sequencing technologies for genome-wide transcriptional analysis of human adult mesenchymal stem cells. The goal of our investigations is to assess functional significance of retro-transcription in age-related decline of human adult stem cell function. A community resource generated in the course of our investigations will empower our research collaboration and the research community to engage in deeper functional analyses of these fascinating genomic elements that will ultimately lead to biologically significant insights in the field of biology of ging.
Understanding of the impact of retrotransposons on the aging portion of our epigenome may be helpful in determining individual susceptibility to age-related diseases through the determination of a molecular age. Focus of this proposal is on transcriptional profiling of SINE/Alu repetitive sequences using RNA-Seq and functional assessment of context-dependent transcription during replicative and genotoxic-stress induced senescence in human adult stem and somatic cells.
|Zhao, Yue-Qiang; Jordan, I King; Lunyak, Victoria V (2013) Epigenetics components of aging in the central nervous system. Neurotherapeutics 10:647-63|