⫸ The cholesterol-lowering drugs, statins, can affect lifespan by reducing the risk of ischemic heart disease. Treatment of Drosophila with simvastatin reduces arrhythmias associated with aging and extends lifespan [172]. Cholesterol-lowering drugs such as simvastatin (38 or other statins) may act directly on antioxidant pathways or telomere shortening to regulate health during aging [173, 174]. However, simvastatin has not been reported to promote longevity in mice [151]. Despite the discouraging results, many case–control studies and clinical trials suggest that statins have shown considerable potential for statins in health and prevention of age-related diseases (e.g., dementia, cancer, etc.) [173].

Simvastatin (10 or 20 mg/kg for 4 weeks) reduced Aβ plaques, neurotoxicity, and proinflammatory cytokines and improved memory in the Morris water maze and Y-maze in diabetic mice [175]. In a mouse model of Alzheimer’s disease, it reduced Aβ neurotoxicity and upregulated brain-derived neurotrophic factor levels in the hippocampus and dentate gyrus [176]. Simvasta- tin was reported to reduce neuroinflammation and Aβ plaques, improve cerebral blood flow, and alleviate oxida- tive stress in amyloid precursor protein mice [177]. Sev- eral large-scale studies for the treatment of dementia and meta-analyses have shown the potential of statins, but conflicting results have also been reported [178]. A post- mortem study showed that statin users had a reduced risk of developing the classic pathology of AD (nerve protuberant plaques or tangles) [179]. Patients between 78 and 85 years of age who took statins lived 2 years longer [180]. Cholesterol levels were not associated with increased longevity in older adults [181]. ⫷[1]