Independent regulation of age associated fat accumulation and longevity
Open accessAbstract
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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Obesity pharmacotherapy in older adults: a narrative review of evidence
Henney, A. E., Wilding, J. P. H., Alam, U., & Cuthbertson, D. J. (2025) · International Journal of Obesity · doi:10.1038/s41366-024-01529-z · Cited by 51 · see citing works
- 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.
- ORCID
- Venue
- Nature Communications
- Published
- 2020-06-03
- Volume
- 11
- Issue
- 1
- Pages
- 2790-2790
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7270101
- 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
- gold
- doi.org
- 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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