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Theories of Ageing > Theories of Ageing > Flashcards

Theories of Ageing Flashcards

1
Q

What is ageing?

A
  • 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
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2
Q

What is longevity?

A

Length of the lifespan independent of the biological ageing process

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3
Q

Why could have longevity evolved?

A

To maximise the opportunities to reproduce

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4
Q

Why could have ageing evolved?

A

Random process

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5
Q

What happens when we age?

A

physiological, pathological and psychological changes

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6
Q

What do program theories suggest?

A

suggest that aging follows a biological timetable

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7
Q

Which are the program theories?

A
  • programmed longevity
  • endocrine theory
  • immunological theory
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8
Q

What is the “programmed longevity theory’?

A

aging arises due to time-dependent changes in expression of key genes involved in growth or development

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9
Q

What is the endocrine theory?

A

hormonal influences (eg GH-IGFI) constitute a biological clock that determines the rate of aging of an organism

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10
Q

What is the immunological theory?

A

progressive loss of immune system activity with increasing age leads to cellular stress and eventual death from impact of disease

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11
Q

What do damage/error theories suggest?

A

the cumulative impact of environmental assaults (external insults (e.g. UV) or intrinsic physiological processes (eg ROS) cause aging

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12
Q

Which are the damage theories?

A
  • wear and tear
  • rate of living
  • cross-linking
  • free radical
  • somatic DNA damage
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13
Q

What is the wear and tear theory?

A

components of cells and tissues eventually wear out

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14
Q

What is the rate of living theory?

A

an organisms rate of basal metabolism determines its lifespan

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15
Q

What is the cross-linking theory?

A

accumulation of cross-linked proteins impairs cellular function, slowing down bodily processes and leading to aging

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16
Q

What is the free radical theory?

A

reactive oxygen species (ROS) cause damage to cellular macromolecules, (DNA, proteins) and organelles, impairing function

17
Q

What is the somatic DNA damage theory?

A

mutations are acquired faster than they can be repaired, so accumulate over time leading to a breakdown of genetic integrity

18
Q

Which are the hallmarks of ageing?

A
  • genomic instability
  • telomere attrition
  • epigenetic alterations
  • loss of proteostasis
  • deregulated nutrient sensing
  • mitochondrial dysfunction
  • cellular senescence
  • stem cell exhaustion
  • altered intercellular communication
19
Q

What is genomic instability?

A
  • 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
20
Q

What is telomere attrition?

A

Telomeres (repeated DNA sequences at end of chromosome) shorten with each round of cell division. When they reach a critical shortness, cells enter senescence

21
Q

What are epigenetic alterations?

A
  • loss of DNA methylation
  • age-specific patterns of histone modification
  • changes in the expression of enzymes that regulate DNA packing - chromatin remodelling
22
Q

What is impaired proteostasis?

A
  • 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
23
Q

What is deregulated nutrient sensing?

A

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

24
Q

What is mitochondrial dysfunction?

A
  • loss of efficacy of the respiratory train with increasing age&raquo_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
25
Q

What is stem cell exhaustion?

A
  • Decline in the regenerative potential of tissues is a key hallmark of aging
  • Cell cycle activity in aged stem cells is reduced&raquo_space; divide less frequently
  • Loss of haematopoietic stem cell activity leads to reduced production of adaptive immune cells, and contributes to anaemia and myeloid cancers
  • May occur due accumulation of DNA damage and telomere shortening
26
Q

What is cellular senescence?

A
  • stable arrest of the cell cycle in response to DNA damage
  • cells removed by the immune system
  • as we get older–> the demand for replacement cells may increase, thus exhausting the capacity of the stem cells
  • also secrete pro-inflammatory cytokines
27
Q

What is altered intercellular communication?

A
  • AGEING–> inflammation, hormonal changes (neuroendocrine dysfunction) , and reduced immune system activity and resultant changes in microbiome (eg gut)
  • Senescent cells can influence those around them to enter senescence too
    –>
    altered intercellular communication
28
Q

What are primary hallmarks?

A

causes of damage

29
Q

What are antagonistic hallmarks?

A

cell or tissue responses to damage

30
Q

What are integrative hallmarks?

A

result of primary and antagonistic hallmarks

31
Q

Which are the primary hallmarks?

A
  • genomic instability
  • telomere attrition
  • epigenetic alterations
  • loss of proteostasis
32
Q

Which are the antagonistic hallmarks?

A
  • deregulated nutrient sensing
  • mitochondrial dysfunction
  • cellular senescence
33
Q

What are the integrative hallmarks?

A
  • stem cell exhaustion
  • altered intercellular communication

Theories of Ageing (1 decks)

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