Ageing Flashcards
What are the 3 groups that the 9 cellular hallmarks of ageing can be grouped into?
Primary hallmarks - cause of damage (-ve)
Antagonistic hallmarks - response to damage (+/-ve)
Integrative hallmarks - link to phenotype of ageing (physiological changes)
What are the 9 cellular hallmarks of ageing?
1) Genomic instability
2) Telomere attrition
3) Epigenetic alteration
4) Loss of proteostasis
5) Mitochondrial dysfunction
6) Deregulated nutrient sensing
7) Cellular senescence
8) Stem cell exhaustion
9) Altered communication
What is genomic instability?
Increased tendency to acquire hereditable genetic alterations that may influence normal function of a cell:
exogenous (UV) or endogenous damage (ROS)
What is telomere wearing?
Result of replication dependent shortening of telomeres that protect the ends of chromosomes from decay and fusion. This leads to genome instability
What is cellular senescence?
Permanent proliferative arrest (cell cycle arrest) on cells in response to various stressors, leading to formation of senescent cells with specific phenotypic characteristics
What is the purpose of cellular senescence?
prevention of progress of damaged cells - trigger removal
With age - exhausted regenerative capacity
Senescence-associated secretory phenotype (SASP): proinflammatory cytokines and MMPs
What is stem and progenitor cells exhaustion?
Inability of stem cells or progenitor cells to replenish the tissue of an organisms
What can cause stem cell exhaustion?
- decline in the ability of stem cells to proliferate
2. excessive proliferation, leading to stem cell exhaustion and premature ageing
What is the effect of ageing on bones?
Dec density, thickness and strength
Dec bone remodelling
Inc adipocyte formation in bone marrow
Dec vit absorption (e.g. vit D)
What is the effect of ageing on joints?
Red cartilage thickness
Excessive collagen cross-linking, leading to inc stiffness and brittleness
Impaired ability of chondrocytes to maintain the surrounding ECM
What is the effect of ageing on muscles?
Atrophy of fat free muscle mass
Red muscle strength
Loss of type II fibres
redistribution of fat depots
What is the effect of ageing on the CNS?
Decline in brain mass and weight
Fewer synaptic contacts and nerve cells
Reduce cerebral blood flow
Altered neurotransmitters
What is the effect of ageing on the PNS?
Decrease spinal motor neurons Axon atrophy Nerve conduction slows Reduced vibratory sensation Reduced thermal sensitivity Loss of myelinated and unmyelinated nerve fibers
What is the effect of ageing on the CVS?
Thickening and stiffening of large arteries - inc systolic + dec diastolic BP
LV hypertrophy
Red sensitivity to sympathetic stimuli
Red maximal O2 uptake
