Hormonal
The rs3758391 C/T single-nucleotide polymorphism in the human SIRT1 promoter determines the magnitude of SIRT1 upregulation in skeletal muscle during long-term calorie restriction, with the T allele facilitating greater expression than the C allele.
If you are following a calorie-restricted diet, your genetic variant rs3758391 in the SIRT1 gene influences how much your muscle's SIRT1 levels rise. Individuals with the T allele (CT or TT genotypes) experience a significantly larger increase in SIRT1 expression after 6 months of restriction compared to those with the CC genotype. This does not mean CC individuals fail to adapt, but their molecular response is blunted. This effect is not seen after only 3 months of restriction, suggesting robust, long-term caloric deficit is required to observe these genetic differences.
Six months of CR or CREX led to a larger increase in skeletal muscle SIRT1 in individuals who had at least one T allele (CT and TT genotypes) when compared with individuals who did not have a T allele (CC genotype)... Thus, this SNP is not associated with a change in baseline SIRT1 expression but does affect upregulation of SIRT1 in response to long-term CR or CREX.
Why this rating
The study combines rigorous in vitro mechanistic data (EMSA, ChIP, reporter assays) with a human clinical cohort, though the clinical cohort is small (n=32) and underpowered for some secondary endpoints.
Source
A single-nucleotide variation in a p53-binding site affects nutrient-sensitive human SIRT1 expression
Asma Naqvi et al. · Human Molecular Genetics · 2010
DOI 10.1093/hmg/ddq331
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