Introduction Flashcards
Is aging a disease
No, it is a normal physiological process
Common diseases associated with ageing
Visual/h earing impairments
Arthritis, physical/mental impairment,
Infections
Définition of ageing
Collection of changes that render humans progressively more likely to die
Senescence
Biological processes and Molecular phenotypes behind the aging process
Triggers of ageing
Stress
Exogenous(Radiations UV etc
Endogenous(ROS
Mechanism of ageing
This triggers cause DNA and cellular damage which can cause cancer. The body response to this by increasing antitumoral genes which block the cell cycle leading to cellular senescence
Cellular mechanism in immune aging
1) cell autonomous (changes in individual cells)
2) population based(alteration in cell renewal)
Mechanism of cell renewal
Immune cells originate from hematopoietic stem cells. However alteration in the process by failure of self renewal, aberrant differentiation, senescence /apoptosis can lead to immune aging over time ,
Molecular mechanism of aging
Accumulation of oxidative radicals, and mitochondria dysfn damages the DNA or shortens the telomeres affecting cell division
Effect of aging on the adaptive immune system
Diversity is shaped by previous encounters with pathogens due to accumulation of memory cells. This causes shrinking of the repertoire increasing susceptibility to new infections
Effects of aging on the primary lymphoid tissue
1)involution of the thymus
2)decrease hematopoietic stem cells in the bone marrow
This leads to decrease release of polyclonal lymphocytes and expansion of oligonal memory cells
Why is there increase baseline Inflammation in aging
Increase release of DAMPs which leads to increase activation of inflammation. This causes impaired pathogen control
Immune senescence
Age related loss of immune function with increase predisposition to emerging infections and poor immune response to vaccine
Xtic of a good study model
Reflect and recapitulate the biological system that it addresses
Types of immune senescence models
Depend on the question.
1) Cell or tissue models for specific cells
2) in vivo studies(involve many cell types) e. g rodent models
3) for diseases specific to humans(use of primates like monkeys)
How to choose your model
Depends on your research question 1) KO(to define molecular mechanism)
2) can your question be addressed by a rodent model
Pros of primate models
1) closely related to humans
2) invivo manipulations might be accepted
3) also have a long lifespan
Cons of primate models
1) expensive
2) strong ethical restrictions, suboptimal availability of reagents
Pros of mouse model
1) can be used to study molecular mechanisms in KO mice
2) quick breeding
3) easy transfer of tissue with limited or no MHC restrictions in inbred
Cons of mouse model
1) phlogeneticaly quite distant from humans
2) Hygiene conditions for breeding are more strict
3) short life span
Anti aging therapy
1) stem cell therapy. Has a high risk tfor cancer
2) Thymic fxn improvement
3) calories or mTor suppressors. Rapamycin extends life span in mice, but can cause immune suppression
2) caloric restrictions reduces aging
