Mouse study: liver SIRT6 loss shortens female lifespan via SULT1E1 and estrogen
In mice with liver-specific Sirt6 knockout, females showed accelerated aging and a 17.60% lower median lifespan, linked to higher SULT1E1 and lower circulating estradiol; males showed a different, catabolic lipid-clearing phenotype. The activator MDL-800 rescued metabolic phenotypes in aged females. [1]
Automatic summary · not editorially reviewed
The key findings
Researchers generated hepatocyte-specific Sirt6 knockout mice of both sexes and assessed lifespan, metabolism, liver tissue and gene expression. [1]
Female knockout mice showed accelerated aging and a 17.60% lower median lifespan; aged males showed a catabolic lipid-clearing phenotype. [1]
In females, hepatic Sirt6 loss raised SULT1E1 and lowered circulating estradiol; MDL-800 suppressed Sult1e1 and rescued metabolic phenotypes in aged females. [1]
The source at a glance
- Study type / format
- Preclinical mouse study (abstract)
- Population / context
- Hepatocyte-specific Sirt6 knockout mice of both sexes
- Summary based on
- Study abstract
- Original publication
- August 5, 2026
Liver Sirt6 knockout mice of both sexes
The researchers generated hepatocyte-specific Sirt6 knockout mice of both sexes and assessed lifespan over time, metabolic profiles, liver tissue changes and gene expression patterns. The question was how SIRT6 acts in the liver in a cell-type- and sex-specific way during aging. This is a mouse study; the abstract does not report sample sizes, follow-up duration or the full methods.
Supporting source [1]
Female mice aged faster; males showed lipid clearing
Female knockout mice showed accelerated aging and a 17.60% reduction in median lifespan, with systemic metabolic decline, visceral fat accumulation and advanced metabolic-associated fatty liver disease. Aged male knockout mice instead showed an enhanced catabolic state and a lipid-clearing phenotype through compensatory reprogramming. In females, loss of hepatic Sirt6 hyperactivated SULT1E1, an estrogen sulfotransferase, and lowered circulating estradiol; this was linked to increased new fat synthesis, genomic instability and cellular senescence. These are associations in mice, not proof of cause in humans.
Supporting source [1]
MDL-800 rescued metabolic phenotypes in aged females
Pharmacological SIRT6 activation with the small molecule MDL-800 suppressed Sult1e1 expression, restored estrogen homeostasis and rescued the age-related metabolic phenotypes in aged female mice. The authors describe a SIRT6-SULT1E1 axis as a sex-stratified therapeutic target against age-related metabolic decline. This is a proposed target from mouse experiments; the abstract does not show human benefit, dosing or safety, and the full text was not reviewed.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. This is a mouse study, so the findings do not establish human lifespan or health benefits, and the abstract reports no sample sizes, follow-up duration, dosing or safety data.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Liu Y, Zhang Z, Wang T, Yang X, Zhang Q, Liu X, Lu X, Zhang J, Feng L. · europepmc.org · August 5, 2026