This document discusses several key physiological traits associated with aging:
Genomic instability causes accumulation of genetic damage to DNA over a lifetime from various sources. Telomere attrition refers to shortening of telomeres each time a cell divides, ultimately limiting it to around 50 divisions. Epigenetic alterations change gene expression through factors like histone modifications and chromatin structure. Loss of proteostasis reduces the cell's ability to regulate protein production, allowing damaged proteins to accumulate. Additional traits discussed include mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, and cellular senescence.
10. Evidence suggests, perhaps they
prolong
the lifespan (triggering survival in
response
to physiological stress).
• ROS increase in parallel to
mitochondrial
attempts to maintain survival?
11. Telomere Attrition erosions
The Hayflick limit is the number of
times a
human cell can divide.
• Most mammalian somatic cells do
not
express telomerase.
• 50 divisions is about the limit.
17. Loss of Proteostasis
• As cells age, they loose the ability to do
quality control on protein production.
•
are associated with loss of proteostasis.
• Accumulation of damaged and
potentially toxic proteins.
18. Deregulated Nutrient Sensing
Multiple nutrient sensing pathways
regulate intake to provide just the right
amount of nutrition.
• Decreased nutrient intake can act to
reduce aging of cells because it slows the
accumulation of damage due to ROS.
• But, also as we age, there is a decline in
nutrient sensing, which in turn ages cells.
• Somewhat of a paradox
20. Neuro-hormonal Signaling Becomes Deregulated
As Inflammatory reactions increase,
they deregulate intracellular signaling.
Renin-angiotensin
system
Insulin-IGF
signaling
Adrenergic
signaling Immunosurveillance
21. Cellular Senescence
The stable arrest of the cell cycle
and associated phenotypic changes.
Cellular senescence is intended to
prevent propagation of damaged
cells and trigger their clearance by
immune system.