endocrinology of ageing Flashcards
hormones- amino acid derivatives
small molecules structurally related to individual amino acids
derivatives of tyrosine - thyroid hormones (secreted by thyroid gland) and catecholamines- secreted by hypothalamus
derivatives of tryptophan- melatonin - secreted by pineal gland
peptide hormones
chains of amino acids
glycoproteins
short polypeptides and small proteins
lipid derivatives
carbon rings + side chains built from fatty acids or cholesterol
eicosanoids- lipid derivatives of arachidonic acid
steroid hormones- structurally similar to cholesterol
intracellular receptors
amino acid derivatives
mitochondrial receptors increase ATP production, nuclear receptor binding activates specific genes
cell membrane receptor
amino acid and peptide hormones
binding triggers signalling cascade involving G priteins, cAMP, cGMP and kinases that alter enzyme activity
intraceullular recpetors
lipid derivatives
binding of hormone receptor complex to dna activates specific gene
hormones + ageing
factors affecting hormone levels in older people
- changes in kidney and liver lead to reduced metabolic clearance (changes how quickly hormones are broken down)
- steroid hormones bound to carrier proteins/albumin- decrease in carrier protein synthesis will reduce serum concentrations are steroids are not water soluble
- increased prevalence of conditions that affect endocine system
- negative feedback regulation may complicate interpretation of changes- some glands may be mroe active to make up for a lack of a hormone
- sleep disturbance may affect prod of hormones with circadian rhythm
- general anatomy can affect production of some hormones
effects of GH
metabolism
-protein synthesis, fat breakdown and glucose production
- high IGF1 associated with increased risk of cancer
- low IGF1 associated with increased risk diabtes, CHD and ostoeporosis
GH + IGF1 and ageing
reduced hypothalamic secreted of GHRH (growth hormone releasing hormone)
no decrease in piruitary somatotroph cells
substantial decline in GH and IGF1 production- both basal and in response to stimulation
pancraeas
pancreatic islets- involved in production of insulin
when blood glucose levels increase, is detected by beta cells, produce insulin and lower glucose by: increasing rate of glucose use, increasing transport of glucose into cells
alpha cells produce glucagon when glucose levels are low
glycation- when glucose levels are too high
glucose uptake
facilitated by insulin
glut4 transported to surface, allowing more glucose to be taken up by the cell
impaired insulin secretion
consequences
- hyperglycemia
- reduce glycogen production
- reduced AA absorption and protein synthesis
- reduced glut4 translocation to membrane
- reduced cellular uptake of glucose
glucose metab + ageing
reduced sensitivity of B cells
less effective insulin
decreased rate of response
less insulin production
less insulin response to glucose tolerance test
insulin resistance
target organs become less sensitive to insulin
less glucose removed for given insulin level
higher blood glucose
intitially compensated by increased insulin secretion
may be related to changes in glut 4 transporter
may be related to inactivity and
type 2 diabetes
affects 1 in 5 older people
impaired insulin secretion and or action
elevated blood glucose levels- increased glycation reactions
microvascular damage contrubutes tp pathology - sensory nerves, retinas, kidneys
risk factors- obesity (visceral fat), age and inactivity
responds to exercise and dietary management
why regular exercise can help
increases glut4 content
increases independent glucose uptake by muscle
higher insulin sensitivity
lower blood glucose
lower insulin
effect of thyroid on peripheral
elevated o2 and energy consumption
increased HR and force of contraction
increased sensitivity to sympathetic stimulation
stimulates RBC formation
accelerates bone turnover
most actions mediated by T3 (more biologivcally active) although T4 is present in larger quantity
thyroxine - t4
thyroid/thyroid hormone +ageing
changing in healthy adults vary
- decreased size of thyroid follicles, fibrosis
- intrafollicular colloid declines but higher prevalence of nodules
- slight decrease in t3 levels, slower clearance
- little change in t4 levels
- reduced peripheral t4 to t3 conversion
hypothyroidism
ageing increases prevalence
- affects 5-10% of older women
- low t4 + elevated tsh
- thought to be result of autoimmune disease
- symptoms - sluggishness, weight gain, intolerance to cold, low HR
treating- increases T4 which would lead to increased t3, decreased tsh, increased metabolic rate
parathyroid glands/hormone
PTH levels increase with age
more marked increase associated with- inadequate dietary calcium, oestrogen deficiency, inadequate vit
D
consequence of hyperparathyroidism- bone loss
adrenal medulla
hormones- adrenalin and noradrenalin
produce vasoconstriction, increased HR, mobilisation of glucose and fatty acids in response to sympathetic stimulation from hypothalamus
changes with ageing
- basal concentrations of adrenaline and noradrenaline increase with age
- response to stimulation decreased with age
adrenal gland
medulla- catecholamines - fight or flight response, increased blood glucose and HR
zona reticularsis- androgens (sex steroids)
zone fasciculate- glucocorticoids eg cortisol, promote glucose synthesis, fat and protein catabolism, anti infllammatory efects
zona glomerulosa- mineralcroticoids eg aldosterone, affect electrolyte compisition
adrenal cortex- DHEA
dehydroepiandrosterone
- weak androgen
- DHEA levels substantially lower with age
- declines associated with reduced muscle and bone mass
- little effect of supplementation
adrenal cortex- glucocorticoids
cortisol
- stress response - anti inflammatory and catabolic effects
- shows substantial circadian variation
- with ageing- increases in basal levels but circadian variation reduces
- increased cortisol production in skin
- cortisol excess may contribute to glucose intolerance, bone loss, memory loss, fat redistribution
