Inflammation and Oxidative Stress in Frailty and Metabolic Disease
Chronic inflammation and oxidative stress go hand in hand, both disruptive of tissue function and health. This is in part because mitochondrial dysfunction, which generates an increased amount of oxidative molecules, can provoke inflammation via the innate immune sensing of damage-associated molecular patterns, such as mislocated mitochondrial DNA fragments. Further, broad mitochondrial dysfunction can push a greater number of cells into a senescent state, in which they produce pro-inflammatory signaling. Other links also exist between these two harmful states.
Both frailty and metabolic syndromes lead to the following consequences: poorer response to physical and/or mental stressors, increased risk of hospitalization, adverse outcomes, institutionalization and premature death. A similar pathogenesis underlies the development of the metabolic as well as the frailty syndrome in the context of oxidative stress and acceleration of inflammation. The disturbance of various metabolic processes on the cellular, tissue, and organ level have demonstrated that the syndromes represent two faces of the same coin.
Through the human lifespan, unfavorable biochemical phenomena accumulate, including increased inflammation and the progression of oxidative stress, which result in the manifestation of clinical dysfunctions and, as a result, premature death. Thus, aging is complicated by disorders such as decreased insulin sensitivity, hyperglycemia, hyperlipidemia or civilization diseases such as diabetes, hypertension, and cardiovascular diseases. Gathered clinical and metabolic conditions are seen in the metabolic syndrome. The main mechanism of pathology in the metabolic syndrome is insulin resistance.
Enhanced inflammation, increased reactive oxygen species (ROS) production and faint antioxidant defense systems are responsible for the improper synthesis, secretion and action of insulin leading to insulin resistance. Moreover, lower insulin sensitivity causes an imbalance toward muscle mass density, relative handgrip force, and decreased level of physical activity with an outcome of sarcopenia and thus leads to the clinical face of frailty syndrome. The aim of this narrative review is to pay attention to the interrelationships between the impact of inflammation, oxidative stress markers, and various metabolic pathways in the development of frailty and metabolic syndromes in elderly individuals, which underlie the pathogenesis of these syndromes.