hallmarks of ageing

Question 1

hallmarks

Answer 1

9 biological mechanisms that meet following conditions
- manifest during normal ageing
- experimental aggravation accelerates ageing
- amelioration retards ageing/ increases healthy ageing

Question 2

mechanisms

Answer 2

genomic instability
telomere attrition
epigenetic alterations
loss of proteostasis
dysregulated nutrient sensing
mitochondrial dysfunction
cellular senescence
stem cell exhaustion
altered intercellular communication

Question 3

genomic instability

Answer 3

may affect nuclear or mitochondrial dna or repair mechanisms
impairments to dna repair mechanisms cause premature ageing in some human syndromes
enhancing dna repair mechanisms mat extend lifespan in animal models

Question 4

epigenetic alterations

Answer 4

alterations in packaging of dna- dna methylation, histone acetylation, chromatin remodelling
affect gene expression, due to exposure to chemicals, ageing, development and diet
dna methylation- increases promoter site methylation and decreases global methylation
histone modifications- decreased synthesis of histones

Question 5

telomere attrition

Answer 5

telomeres shortern with age and progressive shortening leads to senescence and or apoptosis
shorter telomeres have been implicated in genomic instability and oncogenesis
telomeres shorten after multiple replications
enzyme telomerase has the capability to extend the telomere ends, prolonging cell life and potentially inducing immortality- cancer cell hallmark

Question 6

loss of proteostasis

Answer 6

protein homeostasis
ageing cells accumalate damaged and misfolded proteins through a function decline in their protein homeostatsis machinery leading to reduced cellular viability

Question 7

primary hallmarks

Answer 7

causes of damage
genomic instability, telmoere attrition, epigenetic alterations, loss of proteostasis

Question 8

antagonistic hallmarks

Answer 8

responses to damage
deregulated nutrient sensing, mitochondrial dysfunction

Question 9

integrative hallmarks

Answer 9

culprits of phenotype
stem cell exhaustion, altered intercellular communication

Question 10

deregulated nutrient sensing

Answer 10

nutrient sensing pathways
ILS
mTOR
AMPK
sirtuins

Question 11

ILS

Answer 11

insulin/ insulin like growth factor (IGF-1) - signalling glucose sensing- activated by high glucose, decreased activity common with ageing

Question 12

mTOR

Answer 12

mammalian target of rapamycin
sensing of high amino acids, regulate anabolic metabolism, mTORC1 pathway downregulation associated with increased lifespan

Question 13

AMPK

Answer 13

amp kinase
sensing high AMP (signal of low energy) inhibits mTORC1, is downregulated with ageing

Question 14

sirtuins

Answer 14

sensing high NAD+ (low energy), downregulated with ageing secondary to NAD+ depletion

Question 15

mitochondrial dysfunction

Answer 15

sources of damage
nutrient surplus- disruption insulin signalling pathways- ROS accumalation
ROS accumalation- mtDNA damage
mitochondrial dysfunction
reduced biogenesis

Question 16

cellular senescence

Answer 16

affects cell function
- cell division
- morphological
- cell function
- senescene associated secretory phenotype (SASP) may affect neighbouring cells
- may arise through telomere attrition or dna damage response
- senescent cells may be removed by immune survellience/ phagocytosis

Question 17

stem cell exhaustion

Answer 17

HSCs- haematopoiteic stem cells -anemia + myelodysplasia
satellite cells- decreased repair of muscle fibers
MSC- mesenchymal stem cells - osteoperosis, decreased fracture rapire
IESC- intestinal epithelial stem cells- decreased intestinal function

Question 18

countermeasures

Answer 18

clearance of senescent cells
stem cell based therapies
epigenetic drugs
telomere reactivation
elimination of damaged cells

Question 19

theories related to hallmarks of ageing

Answer 19

telomere attrition + cellular senescence= hayflick limit
genomic instability= somatic mutation
mitochondrial dysfunction + stem cell exhaustion= free radical/ reactive oxygen species
loss of proteostasis= glycation/ protein accumalation