Kaeberlein · PLoS biology 2004 · Laboratory genetic and lifespan experiment · n=?

Sir2-independent life span extension by calorie restriction in yeast.

Cited 452 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Bench research / basic science laboratory experiment in yeast model

PubMed 15328540 · doi:10.1371/journal.pbio.0020296 · record verified 2026-08-30

What was done

Investigators tested the lifespan of budding yeast subjected to calorie restriction in combination with genetic interventions (*FOB1* deletion, *SIR2* overexpression, and *sir2*/*fob1* double deletion) to evaluate whether Sir2 activation is required for calorie restriction-mediated longevity.

What was found

The abstract reports no numerical lifespan data, effect sizes, or sample counts. It reports qualitatively that calorie restriction combined with either *FOB1* deletion or *SIR2* overexpression further enhanced lifespan, yielding the longest-lived yeast strain reported to date, and that calorie restriction extended lifespan to a greater extent in cells lacking both Sir2 and Fob1 than in Sir2-positive cells.

Why it matters

These findings challenge the model that calorie restriction operates exclusively through Sir2 activation, demonstrating that calorie restriction and Sir2 function via parallel pathways to regulate lifespan in yeast.

Limits

The study is confined to a unicellular model organism (*Saccharomyces cerevisiae*) where aging mechanisms (such as extrachromosomal rDNA circle accumulation) may not generalize to higher eukaryotes or humans. The abstract omits quantitative metrics, sample sizes, and survival statistics.

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