Antiaging Therapy: A Novel Target for Antilipolytic Drugs
Gabriella Cavallini, Alessio Donati and Ettore Bergamini
Affiliation: Interdepartmental Research Centre on Biology and Pathology of Aging Via Roma 55, I-56126 Pisa, Italy.
Aging has been defined as a gradually decreasing ability to maintain homeostasis and increasing risk to die.
Growing evidence supports malfunctioning with age of quality control system. At an older age, accumulation of altered
macromolecules and membranes may impair cell functioning; accumulation of altered mitochondria and peroxisomes may
boost the yield of ROS per unit of produced energy and accelerate the aging process. Evidence produced that autophagy,
an essential part in cell housekeeping during fasting, may help removal of altered membranes, mitochondria and
peroxisomes selectively and account for the antiaging effects of caloric restriction. Stimulation of autophagy may improve
innate and adaptive immunity; decrease the risk of myopathy, heart disease, liver disease, neurodegeneration and cancer;
and retard aging. Functioning of autophagy may decline in well fed adults and is almost negligible at older age. Induction
of autophagy may result in “cleaner cells” lower in oxidative status and more resistant to injury and disease. The
administration of antilipolytic drugs to fasted animals was shown to intensify autophagy in a physiologically appropriate
manner, to enhance submaximal antiaging effects of low level of caloric restriction, to rapidly rescue older cells from the
accumulation of altered mtDNA and older peroxisomes, to increase urinary 8-OHdG levels, and counteract the age-related
hypercholesterolemia in rodents. In conclusion, benefits of long-lasting stimulation of autophagy and protein and
organelle turnover shows that antilipolytic drugs might find a novel therapeutic application in antiaging medicine.
Keywords: Acipimox, aging, antilipolytic drugs, autophagy, caloric restriction, 3, 5-dimethyl pyrazole, everolimus.
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