**7. References**


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**22** 

*Japan* 

Makoto Goto

**Fenofibrate: Panacea for** 

**Aging-Related Conditions?** 

*Division of Anti-Ageing & Longevity Sciences, Faculty of Medical Technology,* 

Fenofibrate, a selective peroxisome proliferator-activated receptors alpha (PPAR-α) activator, has been primarily developed to treat human dyslipidemia. PPAR modulate the expression of genes involved in lipid metabolism through peroxisome proliferator response elements (Willson et al., 2000). Although fenofibrate became commercially available in 1974 (Fournier, Inc., France), its lipid-lowering action mechanism has not been clarified until the late 1990's, contributing to open new research doors. With respect to the mechanisms of action, the drug with pleiotropic activity may be regarded as a "21st-century agent" (Staels

Fenofibrate as a ligand of PPAR-α exhibits lipid-lowering effects by activating PPAR-α. PPAR-α activators stimulate the β-oxidation of fatty acids in the liver resulting in a decreased availability of fatty acids for triglyceride (TG) synthesis (Schoonjans et al., 1995, 1996a, 1996b). In addition, fenofibrate enhances the production of apo-AI and apo-AII: the major component of HDL by activating PPAR-αand increases plasma level of HDL-C directly (Vu-Dac, 1994, 1995). Thus, the lipid-lowering action mechanism of fenofibrate involves potent TG-reducing and HDL-C-increasing actions. Statins, another type of lipidlowering agent do not show such actions, though statins can inhibit hydroxymethylglutaryl

Furthermore, fenofibrate decreased the level of low-density lipoprotein cholesterol (LDL-C), especially "small dense LDL", which may be a powerful metabolic contributor to

PPAR-α regulates the transcription of lipid-associated genes and various genes involved in homeostasis, suggesting the PPAR-α-mediated pleiotropic activities of fenofibrate. The reports on the pleiotropic activities of fenofibrate has been accumulated in a variety of large-

The studies presumably associated with the anti-aging actions of fenofibrate are reviewed in

The pleiotropic activities other than the lipid-lowering actions reported in clinical practice: the anti-inflammatory, antioxidant, and serum uric acid-reducing actions of fenofibrate are

**1. Introduction** 

et al., 1995).

this article.

**2. Clinical efficacy** 

(HMG)-CoA reductase (Endo A, 1992).

scale, randomized, controlled trials (RCTs).

arteriosclerosis (Superko, 2000).

*Department of BioMedical Engineering, Toin University of Yokohama,* 

