Hahn · Nature metabolism 2019 · controlled animal dietary switch study · n=800 mice

A nutritional memory effect counteracts benefits of dietary restriction in old mice.

Cited 132 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Preclinical animal intervention study

PubMed 31742247 · doi:10.1038/s42255-019-0121-0 · record verified 2026-08-30

What was done

Researchers conducted a dietary switch experiment in 800 24-month-old female mice transitioning either from ad libitum (AL) feeding to dietary restriction (DR) or from DR to AL. Molecular mechanisms were investigated using RNA-seq profiling of liver, brown adipose tissue (BAT), and white adipose tissue (WAT), alongside characterization of aged preadipocytes.

What was found

Switching from DR to AL at old age acutely increased mortality. Conversely, switching from AL to DR caused only a weak and gradual increase in survival. Transcriptomic analysis showed that fat tissue, particularly WAT, exhibited a largely refractory transcriptional and metabolic response to late-onset DR. Chronic DR prevented an age-associated proinflammatory signature in preadipocytes that late-life DR failed to establish. No specific numerical survival rates, hazard ratios, or p-values were provided in the abstract.

Why it matters

This study demonstrates an adipose-tissue-based nutritional memory that constrains the longevity and metabolic remodeling benefits of dietary restriction initiated late in life in mammals.

Limits

The study was conducted exclusively in female mice, so findings may not generalize to males or humans. Exact quantitative survival metrics and effect sizes were omitted from the abstract.

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