Theories of Ageing Flashcards
What is ageing?
- progressive accumulation of changes in the body with the passing of time which increase the probability of disease and death of the individual
- time-related deterioration of the physiological functions necessary for survival and reproduction
- wearing out of the structures and functions that reach a peak during development
What is longevity?
Length of the lifespan independent of the biological ageing process
Why could have longevity evolved?
To maximise the opportunities to reproduce
Why could have ageing evolved?
Random process
What happens when we age?
physiological, pathological and psychological changes
What do program theories suggest?
suggest that aging follows a biological timetable
Which are the program theories?
- programmed longevity
- endocrine theory
- immunological theory
What is the “programmed longevity theory’?
aging arises due to time-dependent changes in expression of key genes involved in growth or development
What is the endocrine theory?
hormonal influences (eg GH-IGFI) constitute a biological clock that determines the rate of aging of an organism
What is the immunological theory?
progressive loss of immune system activity with increasing age leads to cellular stress and eventual death from impact of disease
What do damage/error theories suggest?
the cumulative impact of environmental assaults (external insults (e.g. UV) or intrinsic physiological processes (eg ROS) cause aging
Which are the damage theories?
- wear and tear
- rate of living
- cross-linking
- free radical
- somatic DNA damage
What is the wear and tear theory?
components of cells and tissues eventually wear out
What is the rate of living theory?
an organisms rate of basal metabolism determines its lifespan
What is the cross-linking theory?
accumulation of cross-linked proteins impairs cellular function, slowing down bodily processes and leading to aging
What is the free radical theory?
reactive oxygen species (ROS) cause damage to cellular macromolecules, (DNA, proteins) and organelles, impairing function
What is the somatic DNA damage theory?
mutations are acquired faster than they can be repaired, so accumulate over time leading to a breakdown of genetic integrity
Which are the hallmarks of ageing?
- genomic instability
- telomere attrition
- epigenetic alterations
- loss of proteostasis
- deregulated nutrient sensing
- mitochondrial dysfunction
- cellular senescence
- stem cell exhaustion
- altered intercellular communication
What is genomic instability?
- DNA damage (from exposure to external sources or body processes) is accumulated throughout life
–> - changes in DNA copy number and chromosome stability- mutations in DNA repair enzymes–>premature ageing syndrome
- mitochondrial DNA damage
- changes to nuclear architecture
What is telomere attrition?
Telomeres (repeated DNA sequences at end of chromosome) shorten with each round of cell division. When they reach a critical shortness, cells enter senescence
What are epigenetic alterations?
- loss of DNA methylation
- age-specific patterns of histone modification
- changes in the expression of enzymes that regulate DNA packing - chromatin remodelling
What is impaired proteostasis?
- Proteostasis controls the normal folding and maintenance of proteins in their folded state through chaperone (heat shock protein) activity
- Unfolded proteins are normally targeted for autophagy, or breakdown by the proteosome
- Persistence of unfolded proteins–> aggregation–> age -related disorders
What is deregulated nutrient sensing?
dietary restriction :
- mutations that impair the function of the activity of the Growth Hormone (GH) – Insulin-Like Growth Factor I (IGFI) –> increased lifespan and healthy ageing
- AMPK activated by low energy states, and promotes healthy aging by inhibiting mTOR
What is mitochondrial dysfunction?
- loss of efficacy of the respiratory train with increasing age»_space; less energy for cellular processes
- increased reactive oxygen species (ROS) which can damage cellular macromolecules
- Accumulation of mtDNA mutations may lead to reduced bioenergetics, contributing to a decrease in cellular processes and aging
- Mitochondria may become permeabilized (‘leaky’) with age, triggering apoptosis and inflammation
