(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Neurodegenerative-Diseases

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:

Topics: Adult; Aging; AMP-Activated Protein Kinases; Angiotensin II Type 1 Receptor Blockers; Dose-Response Relationship, Drug; Female; Fluvastatin; Gene Expression; Glucuronidase; Humans; Klotho Proteins; Longevity; Male; Middle Aged; Neurodegenerative Diseases; Placebo Effect; Sirtuin 1; Telomerase; Valsartan

Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including Alzheimer disease. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. Moreover, it is becoming more apparent with additional studies that statins can have deleterious effects in preclinical studies and lack effectiveness in various recent clinical trials. This perspective paper outlines pros and cons of the use of statins in neurodegenerative disorders, with particular emphasis on Alzheimer disease.

Topics: Alzheimer Disease; Animals; Atorvastatin; Cholesterol; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lovastatin; Neurodegenerative Diseases; Pyrimidines; Pyrroles; Quinolines; Rosuvastatin Calcium; Sulfonamides