are accomplished through proper movements of calcium ions. In aging most of these processes decline, and this has suggested the hypothesis that a defective calcium homeostasis may represent an early change responsible for functional decay. The nervous system appears to be very vulnerable to an altered calcium homeostasis since many brain functions depend on many calcium-regulated processes. Within the cell, calcium can be found as bound and free (ionized) and its concentration is maintained at around 10~7 M by complex processes. Intracellular organelles, such as endoplasmic reticulum and mitochondria, sequester calcium that can be extruded across the plasma membrane by energy-dependent transport systems. The equilibrium between uptake and efflux mechanisms across the plasma and organelle membranes balances the set point for calcium concentration within the cell or a given cellular compartment. Specific calcium binding proteins (calmodulin, calbindin, troponin, and vitamin D-dependent protein) as well as negatively charged residues within or at the surface of the cell membranes (sialic acid) can bind calcium and modulate the free cytosolic calcium concentration [Ca2+]i. Changes in any of these aspects of calcium homeostasis may alter calcium-dependent processes. In looking for age-dependent changes in calcium regulation leading to cellular dysfunction, very subtle alterations in the cell's ability to respond to normal stimuli must be investigated since the changes may be so subtle that they are clearly manifest only when cells are severely stressed, for example, by adverse conditions or excessive stimulation.

By taking into account the multiple roles that calcium plays in neurotransmission and intracellular signaling, it appears reasonable to suppose that minor changes in calcium-regulating processes in neurons may result in the alterations affecting cognition and behavior reported in aging. Because of the complexity of the overall cellular calcium regulation, the identification of alterations due to age in calcium-handling systems is a rather difficult task. Direct measurement of intracellular calcium is possible only in isolated cells or tissue slices that do not mirror exactly the actual situation present in the living tissue; therefore, this enables data to be obtained on very discrete aspects of intracellular calcium regulation. Moreover, Ca2+ relays the signals elicited by the first messengers to their omnidirectional destinations: this Ca2+ dynamic signaling involves [Ca2+]i fluctuations within very short time frames (fraction of millisecond) that add further complications in measuring basal levels of calcium even in isolated cells (Chen and Fernandez, 1999). Despite these difficulties, several reports document that in the aging nerve terminals calcium handling is slower and less effective than in terminals from younger laboratory animals. Namely, in aged rats presynaptic Ca2+ signals are prolonged or Ca2+ clearance is slowed; that is, following stimulation the kinetics of the buffering or the clearing of Ca2+ are altered in aging, thus Ca2+ remains elevated for a longer period of time. Considering that calcium regulates metabolic pathways and serves important functions as second messenger, reasonably [Ca2+]i must be tightly regulated.

In agreement with this assumption, the age-related changes in Ca2+ homeostasis just described are supposed to underlie a decline in brain function; however, the complexity of the dynamics of Ca2+ regulation does not allow the interpretation of a prolonged elevation of [Ca2+]i at the old nerve terminals as necessarily deleterious for neuronal function.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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