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Shi Lab
RESEARCH
Germline-Soma interactions play critical roles in the process of aging. Reproductive status profoundly impacts the length and quality of life in species across the evolutionary spectrum. Limitation of reproduction in worms and flies significantly extends their longevity through conserved pathways. Similarly, castration has been shown to increase lifespan in rodents and humans. By contrast, increased reproduction leads to decreased lifespan in many species across taxa through mechanisms that remain substantially unknown.
C. elegans’ mode of reproduction provides a unique opportunity to investigate germline-soma interactions at multiple levels: i) no germline activity (germlineless mutants), ii) low germline activity (hermaphrodites reproducing by self-fertilization with self-sperm), and iii) high germline activity (hermaphrodites mated with males, as mating significantly accelerates germline stem cell proliferation, leading to germline hyperactivity). Removal of the C. elegans germline significantly extends lifespan, increases fat accumulation, and enhances resistance to various stresses. In the Shi lab, we focus on studying the more relevant biological condition of having an ACTIVE germline in the context of aging. Previously, we found that the physiological changes of mated worms are as dramatic as, but mostly opposite to, those of germlineless worms as compared to unmated self-fertilized worms: mating increases brood size, extends reproductive span, causes significant lifespan decrease, and induces shrinking (Figure 1) and fat loss (Figure 2).
In the Shi lab, we are using mated worms as the model to investigate interconnections between reproduction, longevity, and environmental responses. A focus of current work in this lab is understanding the mechanisms underlying interactions between the mated germline and the soma, and how these interactions influence individual’s health and longevity using an interdisciplinary approach combining transcriptome and metabolome profiling with biochemical, genetic, and functional tests.
Figure 2: Mated worms (right) lose a significant amount of fat compared to unmated worms (left). Overall fat storage is indicated by the intesity of Oil Red O staining.
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