Inflammation and Oxidative Stress in Frailty and Metabolic Syndromes—Two Sides of the Same Coin

Abstract

In developed countries, aging is often seen as typical, but it is made complicated by many disorders and co-morbidities. Insulin resistance seems to be an underlying pathomechanism in frailty and metabolic syndromes. The decline in insulin sensitivity leads to changes in the oxidant–antioxidant balance and an accelerated inflammatory response, especially by adipocytes and macrophages in adipose tissue, as well as muscle mass density. Thus, in the pathophysiology of syndemic disorders—the metabolic syndrome and frailty syndrome—an extremely important role may be played by increased oxidative stress and pro-inflammatory state. Papers included in this review explored available full texts and the reference lists of relevant studies from the last 20 years, before the end of 2022; we also investigated the PubMed and Google Scholar electronic databases. The online resources describing an elderly population (≥65 years old) published as full texts were searched for the following terms: “oxidative stress and/or inflammation”, “frailty and/or metabolic syndrome”. Then, all resources were analyzed and narratively described in the context of oxidative stress and/or inflammation markers which underlie pathomechanisms of frailty and/or metabolic syndromes in elderly patients. So far, different metabolic pathways discussed in this review show that a similar pathogenesis underlies the development of the metabolic as well as frailty syndromes in the context of increased oxidative stress and acceleration of inflammation. Thus, we argue that the syndemia of the syndromes represents two sides of the same coin.

The association between oxidative balance score and frailty in adults across a wide age spectrum: NHANES 2007–2018

“…Firstly, the inflammation mediated by monocytes and macrophages is manifested by the up-regulation of the expression of genes of specific stress-responsive inflammatory pathways. 47,48 Excessive ROS in cells may activate the NF-κB pathway, inducing the expression of pro-inflammatory genes and causing systemic inflammation through increased inflammatory mediators. 46 Such an increased inflammatory state may promote protein degradation or indirectly affect physiological systems by influencing important metabolic pathways, playing an essential role in the pathogenesis of frailty.…”

IL-10 and IL-1β Serum Levels, Genetic Variants, and Metabolic Syndrome: Insights into Older Adults’ Clinical Characteristics

“…Metabolic syndrome (MetS) encompasses several metabolic dysregulations, including insulin resistance, atherogenic dyslipidemia, central obesity, T2DM, and hypertension [ 4 , 6 , 8 , 9 , 12 ], sharing many of its characteristics with frailty syndrome, also known as geriatric syndrome [ 32 ]. MetS development results from a complex interaction between genetic, epigenetic, and environmental factors [ 6 , 8 , 12 ].…”

“…IL-10, despite not directly impacting human adipocyte activity, exerts its influence by regulating lipid metabolism and inflammation in adipose tissue [ 37 ]. This indirect effect is crucial, as changes in adipose tissue related to the increased oxidative stress and inflammatory response, likely caused by ROS and proinflammatory adipocytokine production by adipocytes and macrophages, are known to reduce insulin sensitivity [ 32 , 38 ]. Acosta et al [ 37 ] reported that proinflammatory macrophages are the ones that primarily produce IL-10 in obese and insulin-resistant individuals.…”

The Relationship Between Small Dense Low-Density Lipoprotein Cholesterol and Metabolic Syndrome

“…[6][7][8] In addition, these related mechanisms may vary depending on age. 9,10 The components of MetS are not isolated; they interact with each other. In MetS, dyslipidemia is associated with IR and type 2 diabetes, 11 and diagnosed obese patients are often accompanied by dyslipidemia.…”