Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity.

Authors: Flachsbart F; Croucher PJ; Nikolaus S; Hampe J; Cordes C; Schreiber S; Nebel A

Abstract: The SIR2/Sirt1 gene has been demonstrated as regulating lifespan in many model organisms, including yeast, Caenorhabditis elegans and rodents. These findings render the human homologue, SIRT1, a very plausible candidate as a modifier of human life expectancy. We therefore sought to investigate whether common allelic variation in the SIRT1 gene was associated with human longevity. Five single nucleotide polymorphisms (SNPs), distributed across the entire gene, including the promoter region, were genotyped in our extensive DNA collections of 1573 long-lived individuals (centenarians and nonagenarians) and matched younger controls. Four of the markers were haplotype-tagging SNPs (htSNPs) that defined five common haplotypes. No evidence for an association was detected between any of the tested SNPs and the longevity phenotype at the allele, genotype or haplotype levels. These findings, based on an htSNP approach, suggest that there is no noteworthy influence of SIRT1 sequence variation on exceptional human longevity in the German population. However, this does not rule out the possibility that allelic variants in direct regulators or downstream substrates of SIRT1 could play critical roles in extending lifespan in humans.

Keywords: Aged; Aged, 80 and over; Aging/genetics; Case-Control Studies; Female; Genetic Variation; Genotype; Haplotypes; Humans; Longevity/*genetics; Male; Middle Aged; Polymorphism, Single Nucleotide; Sirtuin 1; Sirtuins/*genetics
Journal: Experimental gerontology
Volume: 41
Issue: 1
Pages: 98-102
Date: Nov. 1, 2005
PMID: 16257164
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Citation:

Flachsbart F, Croucher PJ, Nikolaus S, Hampe J, Cordes C, Schreiber S, Nebel A (2006) Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity. Experimental gerontology 41: 98-102.


Lifespan Factors:
  • SIRT1 sirtuin 1

  • Longevity Variant Associations (p-value):
  • rs3758391 (1.0)
  • rs1885472 (1.0)
  • rs2273773 (1.0)
  • rs10997870 (1.0)
  • rs2234975 (1.0)

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