Molecular basis of CNS aging, frailty, fitness and longevity: Amodel based on cellular energetics
The concept of frailty, a decrease in physical function and increasing vulnerability to morbidity and death, is central to the biological study of aging (Fried et al., 2001; Walston, 2004). Genetics, epigenetics, free radicals, aging, disease, and cellular bioenergetics have all been identified as causative elements in frailty. Study of these elements, and their relations, may allow us to develop dynamic models of the age related emergence of physical frailty at the population level (Dirks et al., 2006). A phenotype has been defined for physical frailty (Fried et al., 2001). An area where frailty is less completely studied is the central nervous system (CNS) where a phenotype has not been developed for cognitive "frailty". We attempt to develop such a model by examining the effects of loss of neuronal energetic capacity with age. To develop a model of frailty in the CNS the ability to parametrically describe changes in neuronal frailty and mortality must be examined in the context of the properties of cellular processes involved in energy production. Processes whose contribution to CNS frailty are to be examined include a) shortening of the telomere by oxidative stress, b) cellular bioenergetics involving mitochondrial enzyme, membrane and matrix structure, c) select genes silencing the expression of specific proteins, and d) genomic and non-genomic thyroid hormone (Triiodothyronine (T3)) regulation of mitochondrial structure and function, genesis and cell growth and differentiation. The role of environmental stressors, such as ionizing radiation (IR), in modifying certain rate parameters of cellular bioenergetics may suggest ways to better study and describe such mechanisms in humans. © 2008 Nova Science Publishers, Inc. All rights reserved.
