Why do we age?
Because our cells age
-progressive decline of cell function and lifespan (enzyme and p53 activity)
-accumulation of cellular and molecular damage
-mutations (exogenous and endogenous)
What are some hall marks of cellular aging
What are the main mechanisms of cellular aging
- DNA damage -> Mutations
- Decreased cell replication -> cell loss
- Defective protein -> decreased cell function
Describe DNA damage
-> leads to mutations
-> can have intrinsic (ROS, spontaneous chem reactions)
OR
-> Extrinsic causes
(chemicals, radiation)
Mutations, cell arrested by p53 for DNA repair or apoptosis -> cell loss and cellular dysregularion
Describe decreased cell replication
Cellular senescence - limited capacity of a cell to grow and divide
-stops in nondiving phase of cell cycle (G0) and does not have the cell machinery to move on to G1 (Resting)
-most imporant mechanism of cellular senescence is telomere attrition (progressive shortening of telomeres)
Describe why Telomeres are important for cell aging
Telomeres are short repetitive sequences of DNA at the end of chromosomes - they protect ends from fusion and degredation during replication
The length is maintained by nucleotide addition mediated by telomerase
In terms of telomeres and telomerase, cell division stops when
when telomeres shorten until cell division stops
Describe Telomerase, their activity and how they affect telomeres
They are a special RNA protein complex that uses its own RNA as a template to add more nucleotides to extend the telomere
Germ cells, and stem cells have the greatest telomerase activity as they are rapidly diving and therefore need telomeres present for replication
Somatic cells have decreasing telomeres with increasing cell divisions
Cancer cells have a lot of telomerase for ~exponential growth
Describe defective protein homeostasis
increased telomere attrision (shortening) with aging also causes impaired normal folding and degredation of misfolded proteins- > which can lead to apoptosis and necrosis
