Frailty and the immune system

Abstract

Frailty describes a medical syndrome that confers increased vulnerability to disproportionate changes in health status following minor stressors. With loss of homeostatic reserve in multiple physiological systems, frailty conveys an increased risk of adverse health outcomes. Despite the lack of a clear universal definition, the utilisation of two landmark operational models has allowed a rapid expansion in frailty-centred research.The pathophysiology of frailty is yet to be elucidated in the literature, but a critical role for a heightened inflammatory state is hypothesised. Raised levels of pro-inflammatory cytokines are associated with frailty, with emerging evidence relating their biochemical action with development of the frailty phenotype.Dysregulation of both the innate and adaptive immune system are key components of the frailty syndrome.Remodelling of the T cell compartment and upregulated inflammatory pathways are theorised to propagate the heightened inflammatory state critical in the frailty syndrome. Increased neutrophil counts, in conjunction with ineffective neutrophil migration associated with age, is theorised to produce tissue damage and secondary inflammation conducive of the inflammatory picture in frailty.Beyond the gold standard of the comprehensive geriatric assessment, management of frailty is a fastevolving area of research. Exercise interventions have shown promising results, improving functional ability and showing beneficial immunomodulation. Vitamin D supplementation, with proposed anti-inflammatory effects, nutritional support and pharmacological treatments all provide promising areas for future therapeutic intervention.

Frailty Is Associated With Neutrophil Dysfunction Which Is Correctable With Phosphoinositol-3-Kinase Inhibitors

“…The susceptibility to infections increases with both age and frailty ( 9 , 10 ). Neutrophils are of primary importance during infective challenges, and previous work by our group and others have described neutrophil dysfunction with an individual’s increasing age.…”

The Role of Neutrophil in The Pathophysiology of Frailty Syndrome

“…bukti ini memberikan pemahaman yang lebih dalam tentang peran inflamasi dalam frailty, namun masih ada beberapa pertanyaan yang perlu dijawab. Terutama, belum ada pemahaman yang memadai tentang bagaimana gangguan pada sistem imun bawaan dan adaptif berkontribusi pada patomekanisme sindrom frailty (Drew et al, 2017). Dengan demikian, permasalahan yang muncul adalah bagaimana tepatnya mekanisme patofisiologis ini terkait dengan perkembangan frailty pada populasi lanjut usia.…”

Overview of Hematopoietic Stem Cells in Systemic Cancer Treatment, Aging, Pregnancy, and Radiation Hormesis

“…The theory of immunology states that aging arises from dysregulation of the immune response to foreign antigens and is associated with acceleration of inflammation followed by natural frailty at the end of life [21] [22], and during different somatic diseases including cancer [23]. However, a dramatic decline in T-lymphopoiesis of the old people is primarily dependent on the status of progenitor niches in the BM and thymus [24], which, in turn, become depleted at 40 years of age, with either 100% for the thymus or BM in the lower legs and femurs, or 30% -75% for the BM in bones, sternum, and ribs [25].…”