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Our Research
Background. Metabolic pathways form the fundamental framework of every living organism. The undisturbed operation of the intricate web of cellular metabolism is pivotal for maintaining the well-being of cells, organs, and the entire organism. Ultimately, it determines the duration of a disease-free period, known as the healthspan. Notably, the occurrence of a majority of age-related diseases escalates exponentially as the overall body metabolic rate declines, underscoring the central role of metabolism in determining how long we can sustain good health.
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Ideally, we could counteract this decline by influencing crucial metabolic pathways. However, many metabolic factors remain insufficiently explored in terms of their fundamental functions and whether they play a critical role in regulating our healthspan. This untapped potential not only provides opportunities for gaining knowledge but also holds therapeutic promise for extending human healthspan.
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Our lab actively explores crucial metabolic pathways related to human healthspan using these main approaches:
The majority of cellular metabolic pathways converge in mitochondria, and mitochondria are critical drivers of age-related diseases. There are numerous mitochondrial proteins, lipids and metabolites, which are not direct constituents of oxidative phosphorylation chain, but still have essential function for cells and tissues, as seen in severe pathologies of inborn errors of metabolism.
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How are these other mitochondria-related factors affected with aging? How do they contribute to healthspan duration?
We are utilizing organelle-tailored multiomics analyses, surpassing traditional high-throughput transcriptomic studies. This approach aims to reveal overlooked factors, encompassing crucial aspects like protein, lipid, and metabolite levels, stability, or transport within mitochondria. The ultimate outcome is an understanding of the mechanisms leading to metabolic decline and senescence.
Studying rare diseases with aging-like features has unveiled certain insights into aging biology. In a similar manner, inborn errors of metabolism, known and unknown, might conceive more of these critical aspects, as the same pathways become dysfunctional in aged population. This presents an unexplored opportunity to understand which human-specific metabolic pathways are essential for longevity of various cell types, potentially offering treatments both for specific diseases and age-related conditions in common aging.
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What molecular mechanisms of inborn errors of metabolism are also behind controlling healthspan in the general population?
Utilizing stem cells derived from individuals with inborn errors of metabolism and implementing advanced technologies, we aim to uncover commonalities between disease mechanisms of inborn errors of metabolism and healthspan duration of general population, and develop interchangeable treatments for rare diseases and healthspan extension.
Millions of years of evolution have shaped diverse lifespans and healthspans in organisms, rooted in molecular foundations that were refined through evolutionary engineering. It is plausible that these adaptation mechanisms comprise not only variable DNA repair efficiency or tumor suppressor mechanisms but also certain metabolic adaptations, driving the observed differences in species healthspans.
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What metabolic pathways sustain varying healthspan of different species?
Utilizing stem cells from various mammalian species and leveraging advanced technological alongside high-throughput analysis, our objective is to unveil evolutionary conserved metabolic mechanisms that extend healthspan, with the ultimate goal of applying this knowledge to extend the human healthspan.