Healthy Aging: A Natural Consequence of Adopting a Yoga-based Lifestyle.

Manganese (Mn) is a transition metal that plays many roles in biological systems. Mn‐dependent enzymes include numerous kinases, arginase, pyruvate carboxylase, glutamine synthase, β‐1,4‐galactosyltransferase, and Mn superoxide dismutase (MnSOD). As such, Mn is essential to numerous biochemical processes in intermediary metabolism, neurotransmitter systems, and protein glycosylation and as an antioxidant []. Despite being critical to these fundamental reactions, Mn is also highly toxic, particularly to the nervous system. Therefore, a tightly regulated system of Mn absorption and elimination has evolved to prevent overload of this trace metal. Our understanding of the function of the transporters that are responsible for Mn regulation has been enhanced over the past two decades, primarily with the discovery of three rare genetic disorders, two of which result in Mn toxicity [, , , , ] and one that causes a systemic Mn deficiency [, ]. Following a preliminary section covering the dietary and environmental sources of Mn and the fundamental features of Mn toxicity (manganism), this review will focus on the physiology of Mn uptake and elimination, and the three genetic disorders of Mn transport. Mn is abundant in the Earth's crust, primarily as inorganic compounds. Due to its atomic structure, it can exist in 11 different oxidation states, but Mn and Mn are primarily found in organic compounds in plant and animal systems []. Mn is quite plentiful in plant‐based foods (nuts, whole grains, legumes) and shellfish; for example, whole grain bread contains 2.5 mg/100 g (around 2 ½ slices) []. The recommended dietary allowance for Mn in adults is between 2.5 and 3 mg/day depending on the sex and pregnancy/lactation status []; consequently, a dietary Mn deficiency is quite rare. However, out of concern for avoiding any toxicity from dietary Mn, a recent opinion from the European Food Safety Authority has established a safe level of Mn intake of 8 mg/day []. For individuals with normal metabolism, the likelihood of developing Mn toxicity through dietary exposure is remote. This is not the case for workers in certain occupations such as battery production, welding, mining, and refining, where there is a risk of inhalational exposure to Mn []. After inhalation, Mn may be absorbed via the mucosa in the nasal cavities directly into the bloodstream, and it may also be directly transported from the olfactory bulb to the cerebral cortex. In both circumstances, Mn thereby avoids the regulatory transporters involved in biliary excretion (see below). From the blood, Mn may both diffuse and be transported into the brain, and, given its atomic similarity to iron (Fe), it then accumulates in Fe‐rich brain regions, including the caudate, putamen, globus pallidus, substantia nigra pars reticulata, and subthalamic nucleus [].