Biology of Aging Flashcards
2 theories of aging each for: programmed development and error accumulation
Programmed Development
1. Telomere shortening - chromosomes have telomere end caps, shorten with each replication until critical level = cell senescent
2. Neuroendocrine - changes in production and feedback control of hormones leads to changes of aging
3. Immunological Theory - The immune system is programmed to decline over time, which leads to an increased vulnerability to infectious disease and thus aging and death.
Error Accumulation
1. Oxidative damage - ROS produced through cell metabolism, leads to cumulative DNA, protein and lipid damage
2. Genome instability - accumulate defects in DNA repair mechanisms = genome instability = cell/organ malfunction
3. Wear and tear theory - Like components of an aging car, parts of the body eventually wear out from repeated use, killing them and then the body.
What are the 12 hallmarks of physiologic aging at molecular/cellular level?
- Cellular senescence
- Mitochondrial dysfunction
- Deregulated nutrient sensing
- Altered intercellular communication
- Chronic inflammation
- Stem cell exhaustion
- Dysbiosis
- Genomic instability
- Telomere attrition
- Epigentic alterations
- Loss of proteostasis
- Disabled macroautophagy
What behavioural interventions impacts processes involved in all 12 hallmarks of aging?
Exercise
What is the evolutionary theory of aging?
Evolution deals with the impact of natural selection on reproductive fitness of species
1. Mutation accumulation theory: force of natural selection declines with age as you are no longer able to reproduce, therefore mutations that are neutral in early life but deleterious in later life could accumulate in the population and lead to aging (aging is a non-adaptive trait, so mutations accumulate over time and yield aging phenotype)
2. Antagonistic pleiotropy theory: aging is an adaptive trait, pleiotropic genes (influence multiple traits) affect fitness in antagonistic ways at different stages of life, genes that have beneficial effects on early fitness in young but harmful beyond reproductive years are favoured by natural selection
What is cellular senescence?
A phenomenon where somatic cells irreversibly stop dividing and replicating but do not undergo apoptosis
How is senescence related to aging?
It is a theory of aging
As organisms age = senescent cells accumulate = promote a number of age related diseases
7 potential mechanisms that initiate cellular senescence
- Ionizing radiation
- ROS
- Toxic exposures (chemo)
- Activation of oncogenes
- Lack of further telomeres (Hayflick limit)/replicative senescence
- Low levels of nutrients
- Abnormally high or low levels of oxygen
2 genes that are responsive for establishing and maintaining cellular senescence
p53
p16-Rb
What are 2 theories for cellular senescence?
- Replicative senescence - induced by loss of telomerase activity and critical telomere length
- Genomic damage - response to severely damaged DNA
- Tumor suppression - provide anticancer protection throughout life
2 ways to differentiate senescent from quiescent cells
Senescent cells = permanent arrest of replication, irreversible, undergo phenotypic change and secrete GFs, cytokines, chemokine and proteases
Quiescent cells = reversible, can re enter cell cycle, no change in phenotype
3 examples of non-ageing processes/3 diseases with cellular senescence
- Tumor suppression
- Wound healing
- Embryogenesis
Disease processes - OA
- Glaucoma
- Atherosclerosis
What are telomeres and what is their function in the aging process?
Caps at the end of chromosomes that shorten with each round of cell replication
If cell expresses enough telomerase then it won’t shorten
They eventually hit a critical length (Hayflick limit) and the cell can no longer replicate (cellular replicative senescence)
What evidence supports the telomerase theory?
Telomere length inversely proportional to cell age
Lost faster in people with progenias (condition that inc rate of aging)
Immortal cells (cancer) have constant telomere length
Restoring telomerase enzyme in cells in vitro = increase in replicative life span
Exceptional longevity associated with longer telomeres
Evidence against telomerase theory
Telomere length not related to life span in other species
Telomerase protects against replicative senescence but not cellular triggered by other pathways
Telomerase deficient mice don’t show profound aging defects
Suggested that it is more a defence against cancer
What is the free radical theory of aging?
Highly reactive oxygen derived free radicals (made through respiration), damage protein, lipid and DNA leading to altered structure and functional capacity of cells
Antioxidants neutralize, enzymes inactivate them
