Metabolic control of aging in C. elegans

Aging is a complex process that is characterized by a physiological decline at the cellular and tissue level and it is associated with many diseases. So far, several hallmarks of aging have been identified, and many of them have emphasized the important role of metabolism in the aging process. The objective of this thesis is to elucidate the role of metabolic processes involved in aging. To explore this, we developed a platform for metabolomics analysis in nematode C. elegans, and measured metabolic consequences of in aging models as well as the interactions between genes and the environment (G x E). In order to study the metabolic consequence related to the aging process, I developed and validated a sensitive mass-spectrometry (MS)-based platform for metabolomics studies in C. elegans. This platform was applied in the following three chapters of the thesis and allowed us to investigate metabolic consequence related to aging in different angles. In Chapter 4, We directly compared two long-lived mutant strains, i.e. daf-2 (impaired IIS pathway) and eat-2 (CR model), by whole-genome microarray and MS platforms. In Chapter 5, we studied the contribution of genetic factors on metabolite levels in a natural population of C. elegans and identified several fatty acid metabolism genes. In Chapter 6, we used a candidate gene approach to study the effect of G x E interaction on metabolic process and aging. In the final chapter of this thesis, Chapter 7 and Chapter 8, I summarized all chapters and provided concluding remarks and future perspectives.