immunosenescence
Risk infection
cardiovascular
nerodegenerative diseases
autoimmure
cancar
determinants
genetics
nutrition
sex
race
excersise
Patho exposure
molecular mechanisms
physical barriers
thymic Involution
decreased T and B call
Impaired telomerase activity
cell แบ่งตัวลดลง
weak immune response
Inflammaging
factor
physical inactivity
obesity
psychological stress
Early life adversity
chonic infection
gene
environment
Lifestyle factor
exposune to xenobiotice
Mechanisms controlling inflammaging and immunosenescence
Imbalance
Anti inflammatory น้อย
Pro inflammatory มาก
cytokine หลั่งมากขึ้น
สาร IL3-I3 ,IL - 6, TNF-0 IL8 และ CRP เพิ่มมากขึ้น
cell Proliferation
Metastisis
cellular Senesence
Blood Brain barrier Leakge
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Effect of chronic infections on the development of inflammaging and immunosenescence
เพิ่มขึ้นของ Immunosuppresive path ways
ลดลงของ Immunostimulatory pathways
Molecular and cellar dysfunction
Nuclear factor kappa B (NF-kB)
hypoxia-inducible factor 1 (HIF-1a)
neuralgic
center where pro-inflammatory and anti-inflammatory signalsconverge
ativation promotes a chronic low-grade
inflammatory state (inflammaging)
Lymphocytes B
A generalized reduction of the overall immunity are faithfully recreated during aging, affecting the protection of the elderly against pathogens
ROS
The high levels of ROS
cause oxidation of lipids, proteins, and DNA and innate immune responses
The p38-mitogen-activated protein kinase (p38-MAPK)
pathway regulates the balance between inflammatory and antiinflammatory responses, preventing chronic inflammation and the further establishment of immunosenescence
Lymphocytes T
As aging progresses, T lymphocytes undergo functional changes that impact their function. It has been reported that the number of T lymphocytes decreases during aging
Trends in therapeutic modulation of inflammaging during immunosenescence
Induced pluripotent stem cells (iPSC) have been employed to generate hematopoietic cells
and/or various specific immune cells
administration of cytokine and growth factor cocktails boosted macrophage function
bone marrow transplantation is a widely used
therapy for thymus regeneration
the use of Cdc42 and BATF inhibitors or antioxidants enhances the number and function of lymphoid-biased hematopoietic stem cells
inhibition of dual specific phosphatases 4 boostsmemory CD4+
T-cell function
administration of fibroblast growth factor 7 (FGF7) stimulates naive T-cell production and promotes the removal of dysfunctional cells, thereby restoring thymus function
administration of rapamycin improves
CD8+ T-cell function
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Conclusions
Inflammation is a key factor for the onset and progression of almost all chronic diseases affecting aged individuals Therefore, identification and characterization of the molecular and cellular mechanisms underlying the immune system
dysfunction will surely help to develop effective therapeutic strategies to prevent the negative outcomes of infectious diseases on aged individuals. Recent scientific evidence indicates that different immune system cells, including hematopoietic stem cells, T cells, B cells, NK cells, thymocytes, macrophages, microglia, granulocytes, and dendritic cells, are suitable targets for cellular and genetic therapies. An effective therapy must
combine in a balanced manner immunostimulatory and immunosuppressive strategies, toward a reasonable immune rejuvenation. Given the intricate network of the molecular eventsinvolved in the regulation of inflammation/immunosenescence
Introduction
aging elicits a decline in the immune system,
affecting both the innate and adaptive immunity responses (immunosenescence), which result in increased vulnerability to toxins and pathogens and the establishment of a chronicinflammation state (inflammaging)
inflmmasome Activatiomn
cardiovascular,
kidney, and neurodegenerative diseases, type 2 diabetes mellitus,
cancer, depression, sarcopenia frailty and infectious diseases