Research

Energy balance

Chronic systemic administration of low-dose 2,4-dinitrophenol (DNP) acts as a caloric restriction mimetic by inducing mild mitochondrial uncoupling, which reduces oxidative stress, improves metabolic markers, and significantly extends lifespan in mice.

This research suggests that mild mitochondrial uncoupling can mimic the longevity and metabolic benefits of caloric restriction. In mice, low-dose DNP extended lifespan and improved metabolic health without reducing food intake. However, DNP is toxic at higher doses and is not approved for human use; this paper serves as a proof-of-concept for developing safer uncoupling agents rather than a recommendation for self-experimentation.

GoodSupportsHIGH confidence
Our results demonstrate that mild mitochondrial uncoupling is a highly effective antioxidant strategy, and describe the first therapeutic intervention capable of effectively reproducing the physiological, metabolic and lifespan effects of caloric restriction in healthy mammals.
Camille C. Caldeira da Silva et al. · Aging Cell · 2008

Why this rating

In vivo mammalian study with statistically significant lifespan extension and multiple metabolic endpoints, though limited to one mouse strain.

Source

Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity

Camille C. Caldeira da Silva et al. · Aging Cell · 2008

DOI 10.1111/j.1474-9726.2008.00407.x

mechanism_only · n=60Cited 338×
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DOI resolved against Crossref · corpus check 2026-06-10

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