Aging and Senescence Flashcards
What is aging?
the gradual change resulting in maturation from birth through childhood and adolescence to adulthood
its a decline through middle and old age
what is senescence?
process by which cells permanently exit the cell cycle and stop dividing
- permanent G0
what causes the induction of senescence?
- telomere shortening
- DNA replicative stress
- oncogene activation
- reactive oxygen species - oxidative damage
- DNA damage - cellular or mitochondrial
what makes senscent cells distinct?
they have a distinct phenotype
- growth arrest
- viable/metabolically acite
- resist apotosis
- express a senescene-assocated beta galactosidase enzyme
What are the cell cycle inhibitors that are increased with senescence?
cyclin dependent kinase inhibitors (P21 and P16)
retinoblastoma protein (pRB)
p53 Pathway
what happens to genes involved in cell proliferation?
silenced!
what is Hitchinson-Gilford Progeria Syndrome (HGPS_?
syndrome characterized by accelerated aging!
life span: 12-15 years
what is teh cause of HGPS?
mutation in lamin A gene (nuclear scaffold protein normally)
inadequate support of nuclear envelope
disorganization of chromatin
DNA damage
what are hte mechanisms involved in senescence?
- DNA replication stress
- mitochondira and ROS
- Stem cell theory
what are hte mechanisms involved in senescence?
- DNA replication stress
- mitochondira and ROS
- Stem cell theory
what goes on in the p53 pathway?
- DNa damage
- increase p53
- increase transcription p21
- senescent growth arrest
what goes on in the p53 pathway?
- DNa damage
- increase p53
- increase transcription p21
- senescent growth arrest
what goes on in pRB pathway?
- increase p16
- increase pRB
- inhibition of cell cycle regulators
- replicative senescence
what goes on in pRB pathway?
- increase p16
- increase pRB
- inhibition of cell cycle regulators
- replicative senescence
what 2 principle effects happen to bone in aging?
loss of bone mass
and brittleness
