期刊
AUTOPHAGY
卷 12, 期 2, 页码 261-272出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2015.1127464
关键词
apolipoprotein B; autophagy; C. elegans; fat storage; intestine; life span; lipid metabolism; lipoprotein; TOR; vitellogenin
类别
资金
- K99 award from NIH/NIA [K99 AG042494]
- R00 grant from NIH/NIA [R00 AG042494]
- AFAR Junior Faculty Research Grant
- NIA/NIH [R01 AG038664/R01 AG039756, R01 AG027463]
- NATIONAL INSTITUTE ON AGING [T32AG041688, R01AG038664, R01AG027463, K99AG042494, R01AG039756, R00AG042494] Funding Source: NIH RePORTER
Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis.
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