, Volume 35, Issue 5, pp 1809–1820 | Cite as

Lysine-specific demethylase-1 modifies the age effect on blood pressure sensitivity to dietary salt intake

  • Alexander W. KrugEmail author
  • Eric Tille
  • Bei Sun
  • Luminita Pojoga
  • Jonathan Williams
  • Bindu Chamarthi
  • Andrew H. Lichtman
  • Paul N. Hopkins
  • Gail K. Adler
  • Gordon H. Williams


How interactions of an individual’s genetic background and environmental factors, such as dietary salt intake, result in age-associated blood pressure elevation is largely unknown. Lysine-specific demethylase-1 (LSD1) is a histone demethylase that mediates epigenetic regulation and modification of gene transcription. We have shown previously that hypertensive African-American minor allele carriers of the LSD1 single nucleotide polymorphism (rs587168) display blood pressure salt sensitivity. Our goal was to further examine the effects of LSD1 genotype variants on interactions between dietary salt intake, age, and blood pressure. We found that LSD1 single nucleotide polymorphism (rs7548692) predisposes to increasing salt sensitivity during aging in normotensive Caucasian subjects. Using a LSD1 heterozygous knockout mouse model, we compared blood pressure values on low (0.02 % Na+) vs. high (1.6 % Na+) salt intake. Our results demonstrate significantly increased blood pressure salt sensitivity in LSD1-deficient compared to wild-type animals with age, confirming our findings of salt sensitivity in humans. Elevated blood pressure in LSD1+/− mice is associated with total plasma volume expansion and altered renal Na+ excretion. In summary, our human and animal studies demonstrate that LSD1 is a genetic factor that interacts with dietary salt intake modifying age-associated blood pressure increases and salt sensitivity through alteration of renal Na+ handling.


Age-associated blood pressure regulation Dietary salt Epigenetic regulation LSD1 



We acknowledge the technical assistance of Tham Yao and Paul Loutraris. This work was supported by the National Institutes of Health Grants K23-HL-084236 (to J. S. Williams), HL-104032 (to L.Pojoga), K24-HL-103845 (to G.K. Adler), HL-69208 (to G. H. Williams), and UL1 RR025758-01 (Harvard Clinical and Translational Science Center).

Supplementary material

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Copyright information

© American Aging Association 2012

Authors and Affiliations

  • Alexander W. Krug
    • 1
    • 4
    Email author
  • Eric Tille
    • 1
    • 4
  • Bei Sun
    • 1
  • Luminita Pojoga
    • 1
  • Jonathan Williams
    • 1
  • Bindu Chamarthi
    • 1
  • Andrew H. Lichtman
    • 2
  • Paul N. Hopkins
    • 3
  • Gail K. Adler
    • 1
  • Gordon H. Williams
    • 1
  1. 1.Division of Endocrinology, Diabetes, and HypertensionBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Department of PathologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Cardiovascular Genetics ResearchUniversity of UtahSalt Lake CityUSA
  4. 4.Department of Internal Medicine IIIUniversity Clinic Carl-Gustav-Carus, University of DresdenDresdenGermany

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