senescence Flashcards
primary ageing
intrinsic changes occurring with age, unrelated to disease or environmental influences
secondary gang
changes caused by the interaction of primary aging with environmental influences or disease provcess
wear and tear
free radicals, DNA damage, aggregation of proteins which aren’t cleared, dysfunctional proteins not cleared
processes that cause aging
- damage caused by oxidative stress
- inadequate repair of damage
- dysregulation of cell number
ROS
reactive oxygen species oxidative stress - susceptibility of sugars - glycation - susceptibility of mitochondria - susceptibility of DNA (somatic mutations, may kill the cell or cause problems)
repair mechanisms
DNA - repair, telomeres
protein turnover - ubiquitin, autophagy
membranes - lipid peroxidation
cell number homeostasis
limitations to cell division - senescence - hay flick limit, telomeres
cell removal by - necrosis, apoptosis
cellular senescence
cels in senescence response to damage/replication
- arresting growth of old/dmagaed/dysfunctional cells
- beneficial early in life, may contribute to aging later - altered secretion of proteases, cytokines, growth factors
accumulation og senescent cells predicts lifespan
changes in body composition
decrease in lean body mass, muscular and skeletal mass, decrease in total body water, increase in adipose tissue
cellular changes in aging
increase in DNA damage and decrease in DNA repair capacity
decrease if oxidative capacity
accelerated cell senescences
increase in fibrosis, lipofuscin accumulation (oxidised protein/lipid lysosomes)
sarcopaenia
loss of muscle mass
predominantly type 2 (fast) muscle loss (shift to type 1)
cause of death may be myogenic or neurogenic
muscle fibre may die to to inactivity or MN loss (cannot survive without being innervated by a motor neurone)
two ways muscle fibres die
myogenic - lost due to inactivity
neurogenic - loss due to loss of MN innervation
MN loss
loss of myofibres and loss of fine motor control
cannot be improved with strength training
bone and joints
bone remodelling - Osteoclasts start to win where resoprtion>formation, progressive mass loss, menopause accelerates loss
osteoporosis
decrease in bone mineral density
heightened risk of bone fractures
synovial joints
joint flexibility declines, articular cartilage thins, and decrease in tensile stiffness, fatigue resistance and strength
increase in glycosylation and collagen cross linking, loss of proteoglycans
loss of elasticityy tendency toward osteoarthritis
CNS ageing effect
atrophy
aggressive accumulation
decrease in neurotransmission
PNS aging effect
reduced regenerative response
demyelination/axonal atrophy/electrophysiology
damped signal transduction
loss of responsiveness of autonomic nervous system
less homeostatic ally adaptive
sensory functions
deteriorate
touch, vibration, spatial distinction, proprioception, vestibular function
hearing loss - especially high frequency - loss of organ of Corti hair cells and auditory nerve neurones, decrease in cochlear blood supply
vision in aging
progressive loss of accomodation - presbyopia
decreased ability to alter pupil size in response to light intensity
decreased number of retinal rods and cones
central processing deficit
difficulty distinguishing words from background noise
cognitive functions
intelligence, memory and learning decline is not marked in the baseness of dementia
may reflect slowing of central processing
decrease ability to solve novel problems
learn less quickly
vascular
decrease in arterial compliance and distensibility
cardiac
increase after load due to decrease arterial compliance
decrease ejection fraction, decrease diastolic relaxation
decrease intrinsic and maximum heart rate
increase in atrioventricular conduction time
blunted baroreflex
pulmonary function
decrease respiratory muscle strength and endurance
lung volumes decrease gradually
decrease in lung elasticity (compliance)
exercise capacity
Max O2 uptake declines
decrease muscle mass, CV/pulm function all contribute
elderly CV system - heart less responsive to adrenergics
decrease in response physical conditional
kidney and urinary
RBF and GFR falls wit h age
decrease in renal mass and tubular transport function
lose responsiveness - changes in Na load
decreased bladder capacity
number of uninhibited contractions increases
minor GIT
loss of skeletal muscle at both ends of GIT - minor less of function (chewing, swallowing, faecal continence)
atrophy of secretory systems - decrease of exocrine secretion
decrease in liver mass and hepatic blood flow
endocrine function
increase in insulin resistance and decrease in glucose tolerance
decrease in hypothalamus induce rhythm
increase in ADH release in response to osmolar stimuli
adrenal cortex - cortisol and aldosterone secretion well preserved
thyroid glands - increased incidence of abnormalities, increased PTH levels associated with osteoporosis
growth hormones
significant decline GH and IGF-1 adrenal steroids menopause - abrupt cessation andropause - progressive decline
mechanism of loss of GH
decrease in peak pulsatility of the hypothalamus
GnRH release no longer pulsitile, decrease in plasma GH and IGF-1
adrenal steroids mechanism of reduction
age related decline in zona reticularis cell number
gonads
reduction in hypothalamus stimuli - GnRH
reduction in cell number of gonad secretory cells
- decrease in ovarian reserve, decrease in oestrogen and progesterone
leydig/Sertoli cell atrophy cause decrease in testosterone
decrease in ovarian reserve
decrease in oestrogen
decrease in negative feedback
increase In LH and FSH
increase in follicular recruitment/atresia
reduction in ovarian reserve ceasing oestrogen production
menopause
