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Organ Reserve, Excess Metabolic Capacity, and Aging
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835208/
"Organ reserve" refers to the ability of an organ to successfully return to its original physiological state following repeated episodes of stress. Clinical evidence shows that organ reserve correlates with the ability of older adults to cope with an added workload or stress, suggesting a role in the process of aging. Although organ reserve is well documented clinically, it is not clearly defined at the molecular level. Interestingly, several metabolic pathways exhibit excess metabolic capacities (e.g., bioenergetics pathway, antioxidants system, plasticity). These pathways comprise molecular components that have an excess of quantity and/or activity than that required for basic physiological demand in vivo (e.g., mitochondrial complex IV or glycolytic enzymes). We propose that the excess in mtDNA copy number and tandem DNA repeats of telomeres are additional examples of intrinsically embedded structural components that could comprise excess capacity. These excess capacities may grant intermediary metabolism the ability to instantly cope with, or manage, added workload or stress. Therefore, excess metabolic capacities could be viewed as an innate mechanism of adaptability that substantiates organ reserve and contributes to the cellular defense systems. If metabolic excess capacities or organ reserves are impaired or exhausted, the ability of the cell to cope with stress is reduced. Under these circumstances cell senescence, transformation, or death occurs. In this review, we discuss excess metabolic and structural capacities as integrated metabolic pathways in relation to organ reserve and cellular aging.
Introduction
Organ reserve describes the ability of an organ to endure recurring stressful conditions, especially at a young age, and restore the normal homeostatic balance and function in a relatively short recovery time (Neustadt and Pieczenik, 2008). Part of the age-related decline in physiological functions is attributed to reduction in organ reserve as presented in many of the body systems (Iliodromiti et al., 2016, Goldspink, 2005, Bortz and Bortz, 1996). The functional decline in specific tissues or organs (e.g., immune-, musculoskeletal-, nervous systems) is a key characteristic of aging. Although organs vary in the rate of functional decline with age, this linear decline of reserve capacity with age shows values ranging from 0.5% to 1.4% per year (Bortz and Bortz, 1996, Sehl and Yates, 2001). However, the decline could accelerate by the fifth decade of age (Bortz and Bortz, 1996), which may explain, in part, the age-related increase in vulnerability to disease and infections, complications after clinical procedures, as well as frailty following exposure to stressful conditions (Savji et al., 2013). These observations indicate that aging is characterized by limited organ reserve. The consequences of this decline become evident under stressful conditions.
Given that the damage to mtDNA increases with age, reduced mtDNA stability negatively impacts the reserve capacity of mitochondrial respiration and thus the aging process. Increasing evidence suggests an important role of accumulating mtDNA mutations in the pathogenesis of many age-related neurodegenerative diseases as well as a number of age-related pathological alterations of heart, skeletal muscle, and vascular system (Herrera et al., 2015).
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