Immune system modulation in aging

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