Acetylcholine receptors aging

Red blood cell enzyme activity returns at the rate of red blood cell turnover, which is 1% per day. Tissue and plasma activities return with synthesis of new enzymes. The rates of return of these enzymes are not identical. However, the nerve agent can be removed from the enzymes. This removal is called reactivation, which can be accomplished therapeutically by the use of oximes prior to aging. Aging is the biochemical process by which the agent-enzyme complex becomes refractory to oxime reactivation. The toxicity of nerve agents may include direct action on nicotine acetylcholine receptors (skeletal muscle and ganglia) as well as on muscarinic acetylcholine receptors and the central nervous system. 

One of the most active areas of research in molecular imaging is the study of the effect of age. Suhara and colleagues used PET to study the age-related changes in human muscarinic acetylcholine receptors. In persons between the ages of 18 and 75, uptake of [ C]N-methyl piperidyl benzilate continuously increased in all brain areas with the exception of the cerebellum. The binding of the tracer to acetylcholine receptors in eight brain regions (pons, hippocampus, frontal cortex, striatum, temporal cortex, thalamus, occipital cortex, and parietal cortex) showed an age-related decrease of about 45%. 

Suhara et al. Age related changes in human muscarinic acetylcholine receptors examined with positron emission tomography. Neurosci Lett, 1993. 

A significant age-related decrease in the density of muscarinic acetylcholine receptors was observed on membranes of guinea-pig lungs dissected free of large vessels and bronchi (Suzuki et al. 1985). 

Table 25. Muscarinic acetylcholine receptors in the lungs of male guinea-pigs in relation to age (from Suzuki et al. 1985)...

Nicotine, the major alkaloid fotmd in tobacco plant leaves and the prototypical nicotinic acetylcholine receptor (nAChR) agonist, is known to reduce memory impairment associated with chronic stress [1-3], aging [4—8], brain lesions [9], and cognitive disorders, including Alzheimer s disease (AD) [3, 10-14], schizophrenia [14], attention deficit/hyperactivity disorder (ADHD) [15,16], Parkinson s disease [13, 17], post-traumatic stress disorder (PTSD) [18], sleep deprivation [19, 20], and hypothyroidism [21, 22], Moreover, nicotine is a potent scavenger of hydroxyl and superoxide free radicals. In fact, it has been reported that nicotine is more of an antioxidant than vitamin C [23]. 

Michalek, H., Fortuna, S., Volpe, M.T., et al., 1990. Age-related differences in the recovery rate of brain cholinesterases, choline acetyltransferase and muscarinic acetylcholine receptor sites after a subacute intoxication of rats with the anticholinesterase agent, isofluorophate. Acta Neurobiol. Exp. (Wars)... 

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