Format

Send to

Choose Destination
Int J Mol Sci. 2019 Apr 14;20(8). pii: E1844. doi: 10.3390/ijms20081844.

Expression of Longevity Genes Induced by a Low-Dose Fluvastatin and Valsartan Combination with the Potential to Prevent/Treat "Aging-Related Disorders".

Author information

1
Department of Vascular Diseases, Ljubljana University Medical Centre, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia. miodrag.janic@kclj.si.
2
Department of Endocrinology, Diabetes and Metabolic Diseases, Ljubljana University Medical Centre, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia. mojca.lunder@kclj.si.
3
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SI-1000 Ljubljana, Slovenia. snovakovic@onko-i.si.
4
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SI-1000 Ljubljana, Slovenia. pskerl@onko-i.si.
5
Department of Vascular Diseases, Ljubljana University Medical Centre, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia. miso.sabovic@kclj.si.

Abstract

The incidence of aging-related disorders may be decreased through strategies influencing the expression of longevity genes. Although numerous approaches have been suggested, no effective, safe, and easily applicable approach is yet available. Efficacy of low-dose fluvastatin and valsartan, separately or in combination, on the expression of the longevity genes in middle-aged males, was assessed. Stored blood samples from 130 apparently healthy middle-aged males treated with fluvastatin (10 mg daily), valsartan (20 mg daily), fluvastatin-valsartan combination (10 and 20 mg, respectively), and placebo (control) were analyzed. They were taken before and after 30 days of treatment and, additionally, five months after treatment discontinuation. The expression of the following longevity genes was assessed: SIRT1, PRKAA, KLOTHO, NFE2L2, mTOR, and NF-κB. Treatment with fluvastatin and valsartan in combination significantly increased the expression of SIRT1 (1.8-fold; p < 0.0001), PRKAA (1.5-fold; p = 0.262) and KLOTHO (1.7-fold; p < 0.0001), but not NFE2L2, mTOR and NF-κB. Both fluvastatin and valsartan alone significantly, but to a lesser extent, increased the expression of SIRT1, and did not influence the expression of other genes. Five months after treatment discontinuation, genes expression decreased to the basal levels. In addition, analysis with previously obtained results revealed significant correlation between SIRT1 and both increased telomerase activity and improved arterial wall characteristics. We showed that low-dose fluvastatin and valsartan, separately and in combination, substantially increase expression of SIRT1, PRKAA, and KLOTHO genes, which may be attributed to their so far unreported pleiotropic beneficial effects. This approach could be used for prevention of ageing (and longevity genes)-related disorders.

KEYWORDS:

aging-related disorders; arterial aging; longevity genes; low-dose fluvastatin and valsartan combination

PMID:
31013989
PMCID:
PMC6514706
DOI:
10.3390/ijms20081844
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center