Autophagy-mediated longevity is modulated by lipoprotein biogenesis

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Abstract

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 longlived 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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APA

Seah, N. E., de Magalhaes Filho, C. D., Petrashen, A. P., Henderson, H. R., Laguer, J., Gonzalez, J., … Lapierre, L. R. (2016). Autophagy-mediated longevity is modulated by lipoprotein biogenesis. Autophagy, 12(2), 261–272. https://doi.org/10.1080/15548627.2015.1127464

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