The Tian laboratory is interested in understanding how mitochondrial surveillance mechanisms regulate the aging process. We use C. elegans as a model system, as it has a rapid lifecycle and well-studied genetics. We also explore the physiological consequence of the mitochondrial surveillance signaling pathway in mammalian systems.
Early life mitochondrial stress influences lifespan via epigenetic regulation
Aging is not merely a biological process toward the end of life. Metabolic stress in early life appears to restructure chromatin, leaving a durable epigenetic change that may influence the aging process. We found that mitochondrial stress during early life induces mitochondrial stress response (UPRmt) and longevity via specific epigenetic regulations in C. elegans (Cell, 2016). We further revealed that early life mitochondrial perturbations alter the nuclear epigenome to induce longevity via the histone deacetylation complex NuRD in response to cellular acetyl-CoA levels (Science Advances, 2020).
Inter-tissue coordination of mitochondrial stress response
Neuronal mitochondrial stresses communicate stress signals to peripheral tissues, coordinating organismal-wide metabolic homeostasis for optimal fitness. We found that a secreted Wnt ligand, EGL-20, coordinates mitochondrial stress signaling between neurons and the intestine (Cell, 2018). Furthermore, we found that neuronal mitochondrial stress also communicates to the germ cells, which promotes maternal inheritance of elevated levels of mtDNA via the Wnt signaling, thereby passing down a “stress memory” to offspring. The “stress memory” enables descendants with a greater tolerance to environmental stress and makes the offspring live longer with tradeoffs of delayed development and decreased fecundity (Nature Cell Biology, 2021).
Gut microbiota and aging
All organisms live in a close relationship with their microbiome. The nematode C. elegans represents a great model to study how Microbiota-host interactions shape the aging process.