Ageing Flashcards
What is ageing?
Gradual decline of normal physiological functions in a time-dependent manner.
Leads to impaired function, decreased ability to cope with stressors, increased incidence of age-related conditions and increased vulnerability to death.
What is the link between ageing and disease?
Shift from acute to chronic (non-communicable) disease
Chronic conditions require persistent and long-term management
Increased co-morbidities requires more training and investment for dealing with complex needs
What is the difference between life expectancy and healthspan?
Life expectancy = average length of time an organism is expected to live
Healthspan = percentage of individuals life during which there are generally in good health
What are the hallmarks of ageing defined?
- Should manifest during normal ageing
- Experimental aggravation should accelerate ageing
- Experimental improvement should slow down ageing
What are the 3 groups of cellular hallmarks of ageing?
Primary hallmarks (those causing damage) Antagonistic hallmarks (response to damage) Integrative hallmarks (physiological changes - link to phenotype of ageing)
What are the 4 primary cellular hallmarks of ageing?
- Genomic instability (increased damage/ mutations with no repair)
- Telomere attrition (no replication)
- Epigenetic alteration (loss of translation/ transcription)
- Loss of proteostasis (misfolding/ structural changes)
What are the 3 antagonistic cellular hallmarks of ageing?
- Mitochondrial dysfunction (no energy)
- Deregulated nutrient sensing (reducing nutrient uptake to reduce overload to damaged cells)
- Cellular senescence (frozen in time)
What are the 2 integrative cellular hallmarks of ageing?
- Stem cell exhaustion (no new cells)
2. Altered communication (no coordination)
In what ways can genomic instability occur?
- Changes in genetic code
2. Structural changes that lead to genome instability such as changes in lamins
What are lamins?
Proteins providing structural function and transcriptional regulation in the cell nucleus.
Nuclear lamins interact with membrane-associated proteins to form the nuclear lamina on the interior of the nuclear envelope.
Provide scaffold for chromatin and protein complexes that regulate genomic stability.
What is the free radical theory of ageing?
Ageing caused by accumulation of damage inflicted by Reactive Oxygen Species (ROS)
[Evidence against theory in study in rats where anti-oxidant gene knockout had no impact on lifespan]
What are Reactive Oxygen Species (ROS) molecules?
Highly reactive molecules with the ability to oxidise cell structures causing cell damage, lipid preoxidation and protein modification that can harm the cell integrity
What are telomeres?
Repetitive nucleotide sequences at the end of chromosomes that play a role in protecting the end of the chromosome from decay and fusion with other chromosomes
What is proteostasis?
Protein homeostasis - process by which cells control the abundance and folding of the proteome
What occurs in loss of proteostasis due to ageing?
Load can overwhelm protein quality control (PQC) systems resulting in accumulation of misfolded proteins and loss of protein homeostasis.
Age-associated diseases such as Alzheimer’s and Parkinson’s characterised by aggregations of non-native proteins
What is cellular senescence?
Formation of senescent cells in response to various stressors
[Senescent cells = cells that cease to divide]
What is the purpose of normal cellular senescence?
To prevent progress of damaged cells and to trigger their removal
How is cellular senescence affected with ageing?
Accumulation of senescent cells due to decreased clearance/ exhausted regenerative capacity
What is the stem cell theory of ageing?
Inability of stem (or progenitor) cells to replenish the tissues of an organism,
Can be caused due to stem cell senescence or excessive proliferation leading to stem cell exhaustion and premature ageing.
What happens to the CNS with ageing?
Decline in brain mass
Fewer synaptic contacts and nerve cells
Reduced cerebral blood flow
Altered NTs (e.g. decreased dopamine, 5HT and ACh)
Increased lens rigidity/ lens opacification
Slowed reaction times
What clinical consequences are related to CNS changes with ageing?
Presbyopia (long-sightedness) Cataract Muscle weakness/ atrophy Increased risk of falls Increased risk of delirium
What happens to the respiratory system with ageing?
Reduced lung elasticity and alveolar support
Increased chest wall rigidity
Increased V/Q mismatch
Reduced cough and ciliary action
What are the clinical consequences of respiratory system changes with ageing?
Reduced vital capacity and peak expiratory flow
Increased residual volume
Reduced arterial oxygen saturation
Increased risk of infection
What happens to the cardiovascular system with ageing?
Reduced maximum HR
Dilatation of aorta
Reduced number of pacing myocytes in the SAN
What are the clinical consequences of cardiovascular system changes with ageing?
Reduced exercise tolerance
Widened aortic arch on X-ray
Widened pulse pressure
Increased risk of postural hypotension and AF
What changes can occur to the endocrine system with ageing?
Determination in pancreatic beta-cell function
What are the clinical consequences of endocrine system changes with ageing?
Increased risk of impaired glucose tolerance
What changes can occur to the renal system with ageing?
Loss of nephrons
Reduced glomerular filtration rate
Reduced tubular function
What are the clinical consequences of renal system changes with ageing?
Impaired fluid balance
Increased risk of dehydration/ overload
Impaired drug metabolism and excretion
What changes can occur to the gastrointestinal system with ageing?
Reduced motility
What are the clinical consequences of GI system changes with ageing?
Increased risk of constipation
What changes can occur to bones and muscles with ageing?
Reduced bone mineral density
Loss of skeletal muscle mass and strength
What are the clinical consequences of changes to the bones and muscles with ageing?
Increased risk of osteoporosis
Sarcopenia (loss of muscle mass)
