Obesity, Aging, and Diabetes May Bring Various Influence Including Immune Dysfunction

Bando H

Published on: 2024-12-23

Abstract

In developing medical research, immune dysfunction has been reported from not only autoimmune disease and communicable disease, but also diseases of obesity, aging and diabetes. Furthermore, inflammatory condition has been observed in these diseases. The presence of inflammation is thought to be the key component of immunosenescence, and it may become the leading direct consequence of aging. As related with aging process in the cell metabolism, autophagy has recently attracted attention. Autophagy plays the important role and regulates various immune responses. Obesity, aging, and diabetes share similarities in terms of decreased immune response and also increased chronic inflammation.

Keywords

Obesity; Aging; Diabetes; Inflammation; Immunosenescence; Autophagy

Commentary

For previous medical research, autoantibodies have been studied in detail for autoimmune diseases and also for communicable diseases. Among chronic situation, their roles and mechanism have been investigated in obesity and aging process [1]. As a matter of fact, similar impaired function has been observed in obesity and aging. They include decreased humoral responses or increased persistent inflammation, that may suppress usual immune response, foster autoantigen production, leading to elevated autoantibodies. For these region, therapeutic potential of emerging approaches are included, such as vaccines [2], CAR-T/CAAR-T therapies [3,4], and BiTEs for tackling autoimmune-related mechanism for aging and obesity [5].

The presence of obesity may influence the pathophysiology of wide range of diseases or impaired function, such as diabetes, hypertension, cardiovascular disease (CVD), or non-alcoholic fatty liver disease (NAFLD) [6]. In particular, obesity can increase the incidence and exacerbation of malignant disease, infection, and autoimmunity, associated with worsening vaccine responsiveness. Among these situation, common concept would be the dysregulated immunity as well as inflammation. In obesity or overweight patients, adequate control of cytokine secretion from immune cells shows dysregulation, associated with impaired response of fatty acid metabolism for the inflammation. The inflammatory condition has been often associated with the dysfunction of several ability to keep the consequences of nutritional, physical, chemical and antigenic triggers of any inflammation [7]. The process of immunosenescence can be partially explained by the senescence of organ, tissues, or cells. Then, the hallmarks may be remarkably affected by each pathogenic characteristic from the patient. Consequently, the presence of inflammation is thought to be the key component of immunosenescence, and it may become the leading direct consequence of aging.

Aging has included complex process related with almost all diseases. It is crucial for clarifying molecular aging changes and understanding the mechanism for age-related diseases. Lots of studies have been conducted for linear changes in aging process, but the such diseases and related mortality risk will accelerate after certain point. It indicates the other study rationale of non-linear changes. In the latest report, an impressive result was reported from California area in United States. It has comprehensive multi-omics profiling for longitudinal cohort of 108 residents (25-75 years) [8]. They were followed up for 1.7 years in median and 6.8 years in maximum. As a result, non-linear molecular pattens of aging were found, in which substantial dysregulation occurred about two major points of 44 years and 60 years in chronological age. For detail results, changes around 60 years were observed in cardiovascular disease, carbohydrate metabolism, and immune regulation. Similarly, changes around 40 years were observed in alcohol and lipid metabolism.

From social point of view, aging process has been recognized as important factor influencing all aspects for human and also non-human animal alike [9]. Clarifying the aging concept has provided the foundation of integrating the perspectives of behavioral ecology, evolutionary biology and demography, in order to provide novel insights to social associations and individual social behaviors. It can be adapted for human, mammals, birds, vertebrates and invertebrates. As related with aging process in the cell metabolism, autophagy has recently attracted attention, that is highly preserved in the biological metabolism in eukaryotes [10]. It can degrade damaged organelles, cellular misfolded proteins, and invasive pathogens in the lysosome-dependent manner. From numerous investigations, autophagy plays the important role in some autoimmune diseases, and regulates various immune responses.

Aging changes always include the decreased volume and function of skeletal muscle. Skeletal muscle aging has been a key for contributing the age-related sarcopenia and frailty for substantial implications for general health problems. A recent report showed the in vitro studies [11]. The laboratory specialists profiled 90 thousand single cells and single nuclei from 17 donors. They could map the aging process in human adult intercostal muscle, that identifies the cellular changes in muscle tissue compartment. As a result, apparent subsets of muscle stem cells were found that decreased ribosome biogenesis genes and increased CCL2?C-C motif chemokine ligand 2? expression. It meant the presence of different aging phenotypes.

Diabetes represents a crucial public health concern influencing an impact on human life. Diabetes is known to be characterized as severe skeletal muscle pathology, which can limit functional capacity, QOL and ADL [12]. Lots of reports are found for skeletal muscle regeneration for diabetic patients and animal diabetic models. For effective repair of skeletal muscle due to injury, some necessary condition would be required such as controlling glucose metabolism and inflammation, facilitating regeneration and also limiting fibrotic changes. For diabetic patient, muscle regeneration seems to be not satisfactory compared with healthy case. If the muscle loss would greater than 20%, intrinsic healing function of muscle tissue usually fail to repair the damage. Since diabetes has characterization of severe skeletal muscle pathology, obesity/diabetes patients tend to show certain impact for repairment ability of skeletal muscle when injured. Comparing with males, females may be protected for muscle damage, which is partly from higher levels of estradiol. When exercise-induced muscle damage occurs, male show greater myogenic, inflammatory and myogenic response in comparison with female [12].

Regarding diabetes, various therapy or training may present promising therapeutic modalities to bring the improvement of muscle regeneration [12]. Such methods may include exercise training such as endurance, strength, high intensity interval training (HIIT), dietary supplements, cell therapy, pharmacological treatments, and so on. Concerning most studies of muscle regeneration in diabetes, there are not enough or adequate functional assessments for the research of skeletal muscle. Then, we expect the future development of research in this region, such as in situ, in vivo, in vitro experiments [13].

In summary, obesity, aging, and diabetes share similarities in terms of immune dysfunction, such as decreased immune response and increased chronic inflammation [14]. Research is currently developing in this field. For example, Alzheimer's disease (AZ) is even said to be the third type 3 diabetes (T3D) [15]. Common factors are gradually becoming apparent. It is expected that this article will be of use in the future.

Conflict Of Interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

Journal of Biomedical Science and Research

Obesity, Aging, and Diabetes May Bring Various Influence Including Immune Dysfunction

Abstract

Keywords

Commentary

References