The normal oxidation-reduction reactions occurring in the biological systems, ultimately leads to aging. The side-products of these oxidation reactions are highly reactive free radicals, termed as reactive oxygen and nitrogen species. The latter has immense potential of reacting with and deteriorate biological macromolecules namely lipids, DNA and proteins. In recent years, the free radical theory of aging has gained much importance because of the accumulating evidence that cells of an organism age because of the oxidative stress inflicted upon them. There is a complete balance of free radicals and natural antioxidant defense system inside the body. The body naturally circulates many nutrients and creates antioxidant enzymes having oxidative species scavenging activities, just for the purpose of controlling free radicals and their chain reactions. However, sometimes this innate defense system may not be capable enough to prevent ongoing oxidative damage and the free radicals start attacking the body's own cells, which results in aging. To thwart the latter, a need emerges regarding the exogenous supply of dietary antioxidants, which are believed to play an important role in preventing the expansion of chronic debilitating diseases including aging process.
A wide range of antioxidants are available, known to be effective to slow or stop the aging process by counteracting the free radical induced oxidative stress on cells. Among these, L-deprenyl acts as an antioxidative agent as it can both directly inhibit reactive oxygen species formation by blocking the normal metabolism of biogenic amines and indirectly by activating antioxidant enzyme activity. It is reported, that lower concentration of L-deprenyl is required to prevent oxidative damage than needed to inhibit monoamine oxidase B. In experimental animals, long-term treatment with L-deprenyl enhances the synthesis of SOD1, SOD2 and catalase activity; however, the same does not have a generalized up-regulating effect on antioxidant enzymes. As example, the differential effect on superoxide dismutase activity is seen in the striatum but not in the hippocampus. An increase in the catalase activity is seen in the substantia nigra but not in the striatum along with a decrease in glutathione peroxidase in substantia nigra but has no effect in the striatum. In fact, L-deprenyl acts as an effective antioxidant against hydroxyl radical formation and protects dopaminergic neurons against cell damage induced by neurotoxins. Deprenyl protects neuronal mitochondria against respiratory chain dependent oxygen stress by enhancing the activity of mitochondria-protecting superoxide dismutase and catalase, increases the expression of glutathione peroxidase and preserves the mitochondrial membrane potential. Owing to the fact that mitochondrial dysfunction triggers apoptosis; so L-deprenyl may present an effective prevention of mitochondrial oxidative damage and can reasonably explain for its anti-apoptotic effect in models of neuronal apoptosis. L-Deprenyl counters oxidative stress by reducing lipid peroxidation, protein oxidation etc.
Experimental studies have demonstrated that L-deprenyl treatment in low doses increased the life span of the laboratory animals like aged mice, old male rats, dogs and monkeys but contradictory data are also published. Chronic treatment with L-deprenyl also counters the decline in sexual activity as well as memory decline in aged male rats. L-deprenyl mediates its anti-aging action through a combination of activities: accumulation of lipofuscin, prevention of lipid peroxidation and stimulation of the activities of Glutathione-S-transferase (GST), Na+-K+ ATPase and multiple unit action (MUA) potentials. A reduction of lipofuscin accumulation within the cytoplasm of pyramidal neurons of hippocampus was also reported. Neuroactive agents such as L-deprenyl decrease lipofuscin and ceroid pigment dissolution by cytoplasm rehydration, optimization of the brain cellular recycling system activities. Therefore, L-deprenyl exhibit therapeutic solutions in brain aging deceleration and in age associated diseases.
L-deprenyl induces neuronal differentiation in undifferentiated pluripotent embryonic stem cells (ESCs) in dose-dependent manner and induces neurotrophin expression. This study suggests that both L-deprenyl and stem cell therapy can together be used to improve deficits in neurodegenerative diseases related to aging in future. Therefore, there is a growing interest in applying stem cell therapy in aging. Prophylactic treatment with L-deprenyl may significantly improve the quality of life in the later decades along with a decrease in the susceptibility to age-related neurological diseases. Hence, potentials of this medication, for human use as anti-aging drugs remain worthy of exploration in the future.
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