MicroRNAs: a crossroad that connects obesity to immunity and aging

Abstract

Obesity is characterized by an elevated amount of fat and energy storage in the adipose tissue (AT) and is believed to be the root cause of many metabolic diseases (MDs). Obesity is associated with low-grade chronic inflammation in AT. Like obesity, chronic inflammation and MDs are prevalent in the elderly. The resident immune microenvironment is not only responsible for maintaining AT homeostasis but also plays a crucial role in stemming obesity and related MDs. Mounting evidence suggests that obesity promotes activation in resident T cells and macrophages. Additionally, inflammatory subsets of T cells and macrophages accumulated into the AT in combination with other immune cells maintain low-grade chronic inflammation. microRNAs (miRs) are small non-coding RNAs and a crucial contributing factor in maintaining immune response and obesity in AT. AT resident T cells, macrophages and adipocytes secrete various miRs and communicate with other cells to create a potential effect in metabolic organ crosstalk. AT resident macrophages and T cells-associated miRs have a prominent role in regulating obesity by targeting several signaling pathways. Further, miRs also emerged as important regulators of cellular senescence and aging. To this end, a clear link between miRs and longevity has been demonstrated that implicates their role in regulating lifespan and the aging process. Hence, AT and circulating miRs can be used as diagnostic and therapeutic tools for obesity and related disorders. In this review, we discuss how miRs function as biomarkers and impact obesity, chronic inflammation, and aging. Graphical Abstract

Strategy for Pre-Clinical Development of Active Targeting MicroRNA Oligonucleotide Therapeutics for Unmet Medical Needs

“…However, obesity and MAFLD are multifactorial diseases that cannot be easily controlled by classical therapeutic agents based on the classical one drug, one target mechanism of action. As microRNAs play diverse roles in obesity and metabolic diseases [ 51 , 52 , 53 ], as well as regulate gene functions through a one-to-many relationship, our therapeutic strategy is based on the three following innovative principles:…”

Lifestyle-Driven Variations in Nutrimiromic MicroRNA Expression Patterns across and beyond Genders

“…This observation is in line with our expectations, considering that adipose tissue is involved in a dynamic exchange with miRNAs and serves as both source and target of miRNAs: On the one hand, the adipose tissue itself, especially infiltrated macrophages and T cells, has been shown to be a major source of a range of circulating exosomal miRNAs in the bloodstream [ 43 ]. On the other hand, a variety of miRNAs are known to interact with other adipokines and play an important role in adipose tissue biology [ 38 , 44 , 45 , 46 ]. In the context of obesity, the accumulation of immune cells in adipose tissue increases significantly.…”

Effect of Familial Longevity on Frailty and Sarcopenia: A Case–Control Study

“…Therefore, statistically, they do not meet the confounding criteria. Previous research suggests that both frailty and obesity might be influenced by genes and underlying mechanisms related to inflammation and energy metabolism [ 57 , 68 , 69 , 70 ]. Thus, we understand the lower inflammation, BMI, and frailty prevalence found in our case group are more likely a question of internal consistency than a source of a potential confounding effect.…”