Physiology of ageing Flashcards
1
Q
Most common chronic diseases in elderly
A
Dementia CVD Osteoarthritis Diabetes CAncer
2
Q
Genome instability
A
- Changes in DNA damage
- Genetic damage accumulates as we age through exposure to chemicals, free radicals, radiation etc
- Affects nuclear and mitochondrial DNA
- Base damage - base deletion etc, through mutations/oxidative damage
- DNA adducts: add on to DNA strand e.g. chemicals/UV light
- DNA crosslinks: chemicals cause DNA strands to link = no replication
- Double-stranded break: due to radiation
- Base mis-match: due to mutations
- DNA repair processes become less effective as we age
- Tx: eliminate damaged cells
3
Q
Telomere erosion
A
- Telomere: regions of DNA containing repeat elements at the ends of chromosome
- DNA replication can’t properly replicate the ends of linear DNA
- Telomere repeats added by telomerase (only in germ cells)
- Telomere shortens with age - cells cease proliferation and become senescent
- Telomeres keep ends of chromosomes intact to prevent damage
- Tx: rebuild telomeres on old cells - re-active telomerase
4
Q
Epigenetics and non-coding RNA
A
- Control of gene expression critical for cell function
- These regulatory mechanisms malfunction as we age
- Genes are switched on and off by transcription factors but fine tuning of gene expression occurs by epigenetics (DNA methylation, histone modifications) or by post-translational mechanisms
- Most of these processes are altered as we age
5
Q
Epigenetics
A
- Modifications can be made on DNA (methylation) or on histones (methylation of acetylation)
- Most act to close up chromatin and reduce accessibility to binding proteins (transcription factors, enhancers and insulators)
- Position, level and nature of epigenetic changes alters as we age
- Tx: epigentic drugs causes re-generation
6
Q
Non-coding DNA
A
- Junk DNA produces non-coding RNA that regulates other RNAs
- Levels of NC RNA alter as we age, leading to changes in expression of target genes
7
Q
Nutrient sensing
A
- Allows cells to identify external energy sources and prepare for growth and division
- Metabolic processes damage DNA and proteins in cells = cellular ageing
- Rapamycin (blocks nutrient sensing) increases longevity
- Tx: caloric restriction and pharmacological mimics
8
Q
Cellular senescence
A
- Senescent cells: alive but not growing, altered function and morphology, secrete inflammatory chemicals that affect neighbouring cells
- When you age, senescent cells accumulate as immune system is faulty = diseases like sarcopenia
- Tx: clear senescent cells
9
Q
Changes in proteostasis
A
- Changes in translation, folding, processing etc
- Causes B-amyloid and AD
- Parkin and Parkinson’s disease
- Tx: activate proteolytic systems
10
Q
Mitochondrial dysfunction
A
- Accumulation of mitochondrial DNA leads to defects in respiratory chain dysfunction
- Releases ROS which causes mitochondrial dysfunction too - vicious circle
- Mitochometics and mitophagy = tx
11
Q
Stem cell exhaustion
A
- Number of stem cells fall as we age
- Remaining stem cells may be senescent
- Tx: stem cell based therapies - infusion to repopulate
12
Q
Altered intracellular signalling
A
- Levels of inflammation increase as we age but immune function declines
- An ageing immune system cannot efficiently clear pathogens or senescent cells
- Increased inflammation associated with T2DM, dementia etc
- Blood-bourne rejuvenation factors
