Research
Functional RNA-protein network
As complete transcriptomes have become available in genomes from mammalian species, including human, it has become apparent that a large portion of newly annotated transcripts do not encode protein. These noncoding transcripts include thousands of long non-coding (lnc)RNAs, many of which are emerging as being involved in different cellular contexts, including aging and age-related disorders. RNA-binding proteins (RBPs) and different types of RNAs, including lncRNAs, comprise ribonucleoprotein complexes (RNPs) that play critical roles in all the levels of post-transcriptional gene regulation. Recent studies have shown lncRNA-RBP complexes (lncRNPs) affect gene expression programs by altering transcriptional, post-transcriptional, and post-translational processes, such as chromatin remodeling, transcription factor recruitment, splicing, mRNA turnover, translation, RNA and protein transport, guiding/hindering biochemical interactions, and activating/inactivating specific signaling pathways. In short, lncRNPs provide rich, dynamic, and robust control of cellular structure and function.
Biology of mitochondria in aging
As the primary source of energy, intermediaries of metabolism, calcium signaling, and apoptosis, mitochondria are essential multifunctional organelles in eukaryotic cells. Accordingly, mitochondrial dysfunction severely affects tissue homeostasis and is associated with many age-related diseases, including neurodegeneration, diabetes, cancer, and cardiovascular disease. However, the pleiotropic effects of mitochondria in multicellular organisms make it difficult to understand the basic biology of mitochondria in aging.
Senescence and mitochondrial dysfunction
Senescence is a stress response that limits the proliferation of damaged and/or aberrant cells, and which is suspected to play a role in both organismal aging and declining organ function with age. Accumulating evidence has suggested that mitochondrial dysfunction, given its involvement in the stress response, is closely associated to the cellular senescence. As cellular senescence and mitochondrial dysfunction are broadly understood to be major traits of aging, many researchers have suggested models to explain how those two aging phenotypes are connected to each other. Elucidating the process of ‘cell aging’ at the molecular level, especially within the context of mitochondrial dysfunction, has been a long-standing question in the field of aging research.
Aging and age-related disorders
Considering the essential functions of mitochondria as regulators of cellular homeostasis, and the fact that cellular senescence is triggered when the cellular integrity is abrogated, it is sensible to speculate that certain mitochondria-localized molecules might act as regulators of ‘cell aging’. We hypothesize that a substantial change in the mitochondrial lncRNP network contributes to altering mitochondrial structure and function, thereby perturbing the mitochondrial metabolic program during cellular senescence and organismal aging.
