3479459
Description
Mind Map by Sarah Smith, updated more than 1 year ago
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Created by Sarah Smith
over 8 years ago
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Cell ageing and senescence
- Progerias
- Werner's syndrome
- Ataxia telangiectasia
- Werner's syndrome
- What
changes?
- Expression of proteins and mRNA
- Nuclear and mitochondrial genomes
- MtDNA more exposed to damage: not
complexed with histones, almost all is
coding, repair not as efficient
- cytochrome oxidase is
critically important
- cytochrome oxidase is
critically important
- MtDNA more exposed to damage: not
complexed with histones, almost all is
coding, repair not as efficient
- Energy metabolism
- enlarged mitochondria, decline in
membrane potential, increase in production
of ROS
- enlarged mitochondria, decline in
membrane potential, increase in production
of ROS
- Protein processing
- Glycation - assoc with diabetes and alzeimers
- Protein cross-linking and
advanced glycosylation end
products (AGES)
- Protein cross-linking and
advanced glycosylation end
products (AGES)
- Glycation - assoc with diabetes and alzeimers
- Accumulation of aggregated/damaged proteins and lipids
- accumulation of misfolded proteins and peptides
(amyloid fibrils/plaques) associated with disease
- type II diabetes,
alzheimers, parkinsons
- type II diabetes,
alzheimers, parkinsons
- accumulation of misfolded proteins and peptides
(amyloid fibrils/plaques) associated with disease
- Cessation of division of proliferative cells
- Functional alterations
- Expression of proteins and mRNA
- Network Theory,
Free-Radical Theory,
telomere theory
- Free Radicals
- Reactive Oxygen Species (ROS)
Table 18.1 Page 102
- Hydrogen peroxide
- Lipid peroxide
- Nitric oxide (also RNS)
- Peroxynitrite (also RNS)
- Main source:
oxidative
metabolism
- Superoxide radicals
Fig 18.1 Page 103
- Superoxide radicals
Fig 18.1 Page 103
- Hydrogen peroxide
- Metals (i.e. iron and copper)
- ATOMS OR
MOLECULES WITH
UNPAIRED
ELECTRONS
- Exogenous agents:
UV and ionizing
radiation, some
chemicals
- Effects
- DSBs and altered
bases, i.e.
8-oxoguanosine
- Lipid peroxidation
- Proteins: formation
of carbonyl groups,
3-nitrotyrosine,
amino acid radicals
- Oxidative Stress
- DSBs and altered
bases, i.e.
8-oxoguanosine
- Defenses
- Molecules that scavenge
ROS and RNS
- Proteins that bind metal ions
- Enzymes that convert FRs
to less reactive or inactive
forms
- Table 18.2
Page 106
- Enzymes that repair DNA damage
- Protein degradation systems
- Stress response proteins
- Molecules that scavenge
ROS and RNS
- Reactive Oxygen Species (ROS)
Table 18.1 Page 102
- Replicative Senescence
- Cells cannot divide indefinitely
- Proliferative reserve capacity
- Proliferative reserve capacity
- Senescent cells
- Larger, with larger
nuclei
- Table 18.3 Page 112
- Larger, with larger
nuclei
- Causes?
- Shortening of
telomeres, DNA
damage,
decondensation of
chromatin,
overactivation of
mitotic stimuli and
activation of some
oncogenes
- telomere
shortening doesn't
always occur
- Telomere shortening detected
by ATM results in withdrawal
from the cell cycle and possibly
apoptosis (p53)
- Transfection with genes
for telomerase can make
a cell immortal
- BUT: no correlation between telomere
length and lifespan or replicative
capacity in vitro. Telomere length is
not consistent for all chromosomes in
a cell
- may be "sentinels that respond to
cellular stress - particularly
OXIDATIVE STRESS
- Transfection with genes
for telomerase can make
a cell immortal
- telomere
shortening doesn't
always occur
- Shortening of
telomeres, DNA
damage,
decondensation of
chromatin,
overactivation of
mitotic stimuli and
activation of some
oncogenes
- Cells cannot divide indefinitely
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