Figure 8. Physiological systems promoting frailty.

Frailty involves a multiple organ network that deteriorates with age and features a decline in functional reserves of many physiological systems. There are common impaired responses observed in many organs of the individual with frailty including inflammation, oxidative stress, ectopic fat accumulation, and insulin resistance. The liver is a central player in metabolism and has thus a key role in the aging process. In frailty, there is an increase in de novo lipogenesis that refers to the biochemical synthesis of fatty acids from the carbohydrate catabolism, boosting ectopic fat accumulation. The fatty liver, combined with inflammation and oxidative stress, promotes hepatocyte injury, facilitating fibrosis (collagen production), stem cell activation, and even cancer development. Muscle is also central to the biology of frailty and is the main organ system contributing to the Frailty Phenotype as muscle mass loss and protein degradation trigger weakness, slowness, and weight loss. As compared to subcutaneous adiposity, visceral adiposity is the most detrimental to health due to its pro-inflammatory profile. The increased inflammation, ectopic fat accumulation, and oxidative stress are all risk factors to cardiovascular events by facilitating endothelial dysfunction, aortic stiffness, and clotting. On top of that, increased visceral adiposity and hepatic de novo lipogenesis promote dyslipidemia, which also contributes to cardiovascular dysfunction. Illustrations were obtained on https://smart.servier.com, Published by LES LABORATORIES SERVIER, SAS.