BMS2014 The Biology of Ageing Flashcards
3 evolutionary theories of ageing
- Mutation Accumulation
- Antagonistic pleiotropy
- Disposable Soma
Antagonistic Pleiotropy
Mutations that are beneficial in early life but are detrimental in later life
- not selected against as selection is less efficient later in life
Disposable soma
The trade-off between growth/maintenance /repair and Reprodution -> ageing
accumulation of molecular damage
free radical/oxidative stress
protein/DNA copy errors
glucose, toxins, UV
Hallmarks of ageing
altered intracellular communication
genomic instability
telomere attrition
epigenetic alterations
loss of proteostasis
dereg nutrient sensing
mito dysfunction
cellular senescence
stem cell exhaustion
Rapamycin
inhibits mTOR -> extension of lifespan
Gerontology
the study of biological, psychological and social aspects of ageing in individuals, groups, and populations
Predictors of biological age
Telomere length
epigenetic clock (DNA methylation)
transcriptomic predictors (IL-6, serum albumin)
metabolomic predictors (protein glycosylation)
composite biomarker predictors
Features of poor health in late life
multiple pathologies
geriatric syndromes
risk of dependency
atypical presentation of problems
frequent side effects and complications
limited resillience
5 Is of geriatric illness
Immobility
Incompetence (confusion)
Incontinence
Impaired homeostasis
Iatrogenic disorders
What is physical functioning measured by?
ADLs - Activities of Daily Living
what is mental functioning measured by?
MMSE - mini-mental examination scale
- 30 questions covering orientation, short and long term memory
Sarcopenia
loss of muscle strength, mass, function
sarcopenia aetiology
insulin resistance
inflammation
reduced hormones
mitochondrial defects
oxidative stress
imbalance between pro- and anti-oxidants in the cell -> accumulation of oxidative damage
ROS
reactive oxygen species
RNS
reactive nitrogen species
free radical
any molecular species with unpaired electrons that can exist independently
- take an electron from a target molecule (oxidation)
- highly reactive
Cell’s primary defence against ROS
Antioxidants
Enzymatic Antioxidants
SODs: superoxide dismutases
catalase
GPX: Glutathione peroxidases
TRX: thioredoxins
non enzymatic antioxidants
lipid soluble: VitE, Carotenoids, Q10
water-soluble: VitC, GSH, uric acid
metal chelators
DNA repair mechanisms
BER: Base excision repair
NER: nucleotide excision repair
mismatch repair
double strand break repair
2 secondary defences against ROS
1 chaperone-ubiquitin-proteasome system
2 lysosome
