Cited by 33Genetics, Aging, and Longevity in Model OrganismsLipid metabolism and biosynthesisSirtuins and Resveratrol in Medicine

Independent regulation of age associated fat accumulation and longevity

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Beas, Anthony O., Gordon, Patricia B., Prentiss, Clara L., Olsen, Carissa Perez, Kukurugya, Matthew A., Bennett, Bryson D., Parkhurst, Susan M., Gottschling, Daniel E.·2020·Nature Communications

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 s hikimate and a romatic 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.

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Authors
Beas, A. O., Gordon, P. B., Prentiss, C. L., Olsen, C. P., Kukurugya, M. A., Bennett, B. D., Parkhurst, S. M., & Gottschling, D. E.
Affiliations
  • Fred Hutch Cancer Center (US)
  • National Institutes of Health (US)
  • Worcester Polytechnic Institute (US)
  • Calico Life Sciences (US)
Corresponding author
Beas, Anthony O.
Venue
Nature Communications
Published
2020-06-03
Volume
11
Issue
1
Pages
2790-2790
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3032563275
Cited by
33
References
45
Citations by year
2026: 3 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 9 · 2020: 2
FWCI
1.57
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Washington (P30 CA015704)
  • National Institutes of Health (CA015704, AG023779)
  • National Institute on Aging (R01AG023779, R37AG023779)
  • National Cancer Institute (T32CA009657, CA015704, P30CA015704)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
lipid droplets, aging, longevity, lifespan extension, kynurenine pathway, NAD biosynthesis, shikimate pathway, aromatic amino acid biosynthesis, tryptophan, glycolytic flux, stress tolerance, Saccharomyces cerevisiae
MeSH terms
Cold Temperature, NAD, Saccharomyces cerevisiae, Shikimic Acid, Stress, Physiological, Saccharomyces cerevisiae Proteins, Lipid Metabolism, Biosynthetic Pathways, Metabolome, Lipid Droplets

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