University thesis:
Dissertation, Friedrich-Schiller-Universität Jena, 2019
Footnote:
Tag der Verteidigung: 09.08.2019
Zusammenfassungen in deutscher und englischer Sprache
Description:
Aging is doubtlessly one of the most complex and multi-factorial biological processes we have encountered since the beginning of modern life sciences and the systematic study of human and animal biology. Despite many remarkable findings, aging remains an incompletely understood mechanism, causing several severe diseases, such as cardiovascular diseases, neurodegenerative diseases or cancer. It is associated with a progressive loss of cell functions that lead to a decline of tissue functions and finally resulting in death. Uncountable studies were performed over the last five decades to identify possible causes of how and why we age. Nevertheless, there is a still ongoing debate about the true molecular source of aging, giving rise to a variety of competing theories. Due to its highly complex nature, we have investigated aging from various perspectives, based on the gene expression of different species and tissues. We analyzed a huge set of RNA-Seq transcriptomic data to obtain new insights into the genetic regulation of aging and to identify conserved molecular processes that might be responsible for aging-related disorders. We found that each tissue shows its own distinct pattern of gene expressional changes with age, because they have to respond to different types of stress over time, leading to differing sources of molecular damage and subsequent stress responses. In particular, we could show this for four wellstudied aging-related processes: cellular senescence, inflammation, oxidative stress response and circadian rhythms. In addition, we could show that alternative splicing (i.e., the generation of multiple mRNA isoforms from single genes) is in general only slightly affected by aging and probably plays a secondary role in the overall aging process. In contrast, we found microRNAs (very small regulatory RNA molecules) to be important modulators of aging in all investigated pecies and tissues. Concluding, the results presented in this thesis describe aging as a stochastic process, leading to an accumulation of different kinds of molecular damage and the respective cellular stress responses. We have identified several genetic factors that could serve as potential diagnostic markers or even therapeutic targets, that could help in the future to slow down the progression of age-associated disorders or preventing them. Nevertheless, the subject of aging remains a challenging research field and many open questions still wait to be answered.