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Independent regulation of age associated fat accumulation and longevity

Author

Listed:
  • Anthony O. Beas

    (Fred Hutchinson Cancer Research Center)

  • Patricia B. Gordon

    (Fred Hutchinson Cancer Research Center
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Clara L. Prentiss

    (Fred Hutchinson Cancer Research Center)

  • Carissa Perez Olsen

    (Fred Hutchinson Cancer Research Center
    Worcester Polytechnic Institute, Department of Chemistry and Biochemistry)

  • Matthew A. Kukurugya

    (Calico Life Sciences LLC
    University of California Berkeley)

  • Bryson D. Bennett

    (Calico Life Sciences LLC)

  • Susan M. Parkhurst

    (Fred Hutchinson Cancer Research Center)

  • Daniel E. Gottschling

    (Calico Life Sciences LLC)

Abstract

Age-dependent changes in metabolism can manifest as cellular lipid accumulation, but how this accumulation is regulated or impacts longevity is poorly understood. We find that Saccharomyces cerevisiae accumulate lipid droplets (LDs) during aging. We also find that over-expressing BNA2, the first Biosynthesis of NAD+ (kynurenine) pathway gene, reduces LD accumulation during aging and extends lifespan. Mechanistically, this LD accumulation during aging is not linked to NAD+ levels, but is anti-correlated with metabolites of the shikimate and aromatic amino acid biosynthesis (SA) pathways (upstream of BNA2), which produce tryptophan (the Bna2p substrate). We provide evidence that over-expressed BNA2 skews glycolytic flux from LDs towards the SA-BNA pathways, effectively reducing LDs. Importantly, we find that accumulation of LDs does not shorten lifespan, but does protect aged cells against stress. Our findings reveal how lipid accumulation impacts longevity, and how aging cell metabolism can be rewired to modulate lipid accumulation independently from longevity.

Suggested Citation

  • Anthony O. Beas & Patricia B. Gordon & Clara L. Prentiss & Carissa Perez Olsen & Matthew A. Kukurugya & Bryson D. Bennett & Susan M. Parkhurst & Daniel E. Gottschling, 2020. "Independent regulation of age associated fat accumulation and longevity," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16358-7
    DOI: 10.1038/s41467-020-16358-7
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