|Secretariat, Alumni Association, IDAC|
|Date||Wednesday, March 14, 2018 (17:00 – onwards)|
|Room||7th Floor, Seminar Room 1, Center for Basic Aging Research, IDAC|
|Title||Nutrient sensing mechanisms that mediate lifespan extension|
|Speaker||T. Keith Blackwell|
|Affiliation||Joslin Diabetes Center and Harvard Medical School Department of Geneticsical Sciences, Kumamoto University|
|Organizer||Hozumi Motohashi (Department of Gene Expression Regulation・ext 8550)|
|Abstract||Eukaryotic lifespans can be extended when nutrient or growth-related signaling is reduced. The mTORC1 (mechanistic target of rapamycin) kinase integrates nutrient and anabolic signals to regulate growth. Lower mTORC1 activity extends lifespan, and is central to the benefits of dietary restriction (DR). Reduced insulin/IGF-1 signaling (rIIS) also extends lifespan, from C. elegans to mammals.
mTORC1 drives protein synthesis, but our understanding of how it might control other growth-related processes is limited. Using a systems biology approach, we have determined that mTORC1 broadly regulates mRNA splicing. Through this evolutionary conserved pathway, mTORC1 extends its regulation of protein synthesis, and expands its reach to control many other growth and metabolism parameters. Our findings illuminate how mTORC1 influences growth, development, disease, and the maintenance of gene expression fidelity during aging.
We find in C. elegans that another key element in DR is modulation of a conserved innate immunity pathway that is controlled by p38 signaling. This essential immunometabolic pathway responds to nutrients as well as pathogens, and must be down-regulated for lifespan extension from DR or reduced IIS (rIIS). Unexpectedly, through tissue-non-autonomous action of the DAF-16/FOXO transcription factor, rIIS decreases feeding, and induces a DR-like state that lowers immune activity. Our findings predict that nutrient regulation of immunity will be important for longevity in higher organisms, and reveal an unexpected appetite regulatory function of FOXO.