Cells and Immunity
Week 9
Dr Mike Fry
Ageing
The Ageing Process;
- Characterized by progressive time dependent loss of physiological integrity =
impaired function, increased vulnerability to death. Deterioration is primary risk
factor for human pathologies [cancer, diabetes, cardiovascular, neurodegenerative
diseases]
- Discoveries; rate of ageing is controlled by genetic pathways and biochemical
processes
Hallmarks of Cancer;
- Evading growth suppressors / avoiding immune destruction / enabling replicative
immortality / tumor promoting inflammation / activating invasion and metastasis /
inducing angiogenesis / genome instability and mutation / resisting cell death /
deregulating cellular energetics / sustaining proliferative signalling/
Hallmarks of Ageing;
- Each hallmark fulfills the criteria that;
a. Should manifest in normal ageing
b. Experimental aggravation should accelerate ageing
c. Experimental amelioration [slowing down] should slow normal ageing = increase
healthy lifespan.
- Goals; understand contributions of certain hallmarks and identify pharmaceutical
targets to improve human health [with minimum side effects]
- Grouped into 3 categories;
1. Top; primary hallmarks are causes of cellular damage
o Telomere attrition / epigenetic alterations / loss of proteostasis/ genomic
instability
2. Middle; compensatory/antagonistic responses to damage. Initially mitigate
damage but if chronic, deleterious themselves
o deregulation of nutrient sensing / mitochondrial dysfunction / cellular
senescence
3. Bottom; integrative hallmarks, end result of two previous groups, responsible for
functional decline associated with ageing.
o stem cell exhaustion / altered intercellular communication
Common features of Ageing and Cancer;
- Cancer is consequence of increased gain of cellular fitness, aging is a loss of fitness
- Time dependent accumulation of cellular damage = general cause of ageing
- Cellular damage may prove advantageous [cancer]
- Pathologies associated with ageing involved in uncontrolled overgrowth or
hyperactivity.
Genomic Alterations;
Week 9
Dr Mike Fry
Ageing
The Ageing Process;
- Characterized by progressive time dependent loss of physiological integrity =
impaired function, increased vulnerability to death. Deterioration is primary risk
factor for human pathologies [cancer, diabetes, cardiovascular, neurodegenerative
diseases]
- Discoveries; rate of ageing is controlled by genetic pathways and biochemical
processes
Hallmarks of Cancer;
- Evading growth suppressors / avoiding immune destruction / enabling replicative
immortality / tumor promoting inflammation / activating invasion and metastasis /
inducing angiogenesis / genome instability and mutation / resisting cell death /
deregulating cellular energetics / sustaining proliferative signalling/
Hallmarks of Ageing;
- Each hallmark fulfills the criteria that;
a. Should manifest in normal ageing
b. Experimental aggravation should accelerate ageing
c. Experimental amelioration [slowing down] should slow normal ageing = increase
healthy lifespan.
- Goals; understand contributions of certain hallmarks and identify pharmaceutical
targets to improve human health [with minimum side effects]
- Grouped into 3 categories;
1. Top; primary hallmarks are causes of cellular damage
o Telomere attrition / epigenetic alterations / loss of proteostasis/ genomic
instability
2. Middle; compensatory/antagonistic responses to damage. Initially mitigate
damage but if chronic, deleterious themselves
o deregulation of nutrient sensing / mitochondrial dysfunction / cellular
senescence
3. Bottom; integrative hallmarks, end result of two previous groups, responsible for
functional decline associated with ageing.
o stem cell exhaustion / altered intercellular communication
Common features of Ageing and Cancer;
- Cancer is consequence of increased gain of cellular fitness, aging is a loss of fitness
- Time dependent accumulation of cellular damage = general cause of ageing
- Cellular damage may prove advantageous [cancer]
- Pathologies associated with ageing involved in uncontrolled overgrowth or
hyperactivity.
Genomic Alterations;
