T1 L12 :EFFECTS OF AGE AND DIETON ENDOCRINE FUNCTION Flashcards
what are the phenotypic effects of ageing
5marks
- Increase fat mass, decreased visceral fat
- Sarcopaenia
- Decreased Bone mineral density
- Decreased QOL / mood
- increased risk cardiovascular disease
what are the 2 main features of ageing
Hypogonadism / growth hormone deficiency / aging
what are the nutritional stats with age ( Weight, lean body mass and Diet )
1- Increase from mid-30s
stabalise 50 – 70
2-Decrease by 6-8% / decade from mid-30s
3-Diet - Trend towards decrease in the intake total energy & protein with increasing age
what occurs to your insulin and glucose levels with age
increased insulin and glucose conc with age.
More insulin resistance and so less peripheral glucose uptake
What happens to metabolic syndrome with age
Prevalence Increases
what are the 2 main areas of gonadal axis research
Menopause
Testosterone
what is menopause
Ovarian failure
what occurs to estrogen levels during menopause
pre and post
and what happens to E2 LH and FSH
Pre-menopausal: cycling
Post-menopausal: very low constant levels:
-decreased E2, but increased LH and FSH
what are the symptoms of menopause
and what is the mean duration
Hot flushes, night sweats
Median duration of menopausal symptoms 7 years
what causes morbidity in menopause
increased osteoporosis
increased CHD
increased sexual dysfunction
what is HRT
Hormone replacement therapy - used as a treatment of symptoms of disorders associated with oestrogen deficiency like osteoporosis )
what are the benefits of POST-MENOPAUSAL HRT
decreased osteoporosis and therefore fracture risk
Decreases menopausal symptoms
what are the risks of POST-MENOPAUSAL HRT
-increase in venous thrombo-embolism
-Increase in breast Ca (small)
esp > 5 years
- Increase in endometrial Ca
- –if use unopposed E2
what occurs in the male gonadal axis
and give a rough statistic of what happens at 75 years compared with 25
a gradual decrease in testosterone associated with increasing age
at 75 years 2/3rds that of @ 25 years
what are the effects of low testosterone in men
poor libido
increase in osteoporosis
decrease in muscle strength
what are the effects of testosterone treatment on bone
increase in bone mineral density of hypogonadal but bisphosphonates work independent of the androgen status
what happens to the body composition with the male gonadal axis with testosterone treatment
advantages
decrease fat mass
increase in lean mass
what is there little to no evidence of testosterone treatment improving
Atherosclerosis
sexual function
cognitive function
Mood/quality of life
what does weight loss improve
levels of testosterone
what happens to the GH-IGF-I axis as you age
GH and IGF-I decreases with age
but still wide variation
what does GH treatment do to body composition
- increases lean body mass
- decreases fat mass
what doesn’t change significantly with GH treatment
- Bone mineral density
- Lipids
what are the risks with GH treatment
- Cancer I increased IGF-I assoc with non-smoking cancers-prostate, coon, breast
- Increase in T2 DM
what are the side effects of GH treatment
- Soft tissue oedema
- Arthralgias
- Carpal tunnel syndrome
what happens with cortisol as you age
there is an increase in the levels- trough levels also increase
phase advance of diurnal rhythm (Troughs and peaks occur earlier)
what is the Sapolsky’s glucocorticoid cascade hypothesis
- decrease in hippocampal glucocorticoid & mineralocorticoid receptors
- decrease sensitivity to glucocorticoid negative feedback
- increase in glucocorticoids
leading to hippo campal neurons vulnerable to damage
‘feed forward cascade’
what happens to DHEAs with age
they decrease with age
(helps to protect against CHD)
therefore a low DHEA: low]:cortisol ratio found in cancer, inflammatory diseases, T2DM, CV disease
what does DHEA have no evidence of effect on
- body comp
- physical performance
- Insulin sensitivity
what does increasing age do to thyroid hormone biomarkers
increase in TSH
T4 same
decrease in T3
decrease in peripheral T4-T3 conversion
what does starvation do to gluc-insulin levels
It decreases them and increases insulin sensitivity
what is Leptin produced by
It’s produced by white adipose tissue
what does starvation signal do to leptin and to hypothalamus
It signals energy availability
Decrease leptin- Increase food uptake and decreased energy expenditure
decreased leptin leads to decrease fertility
what does starvation do to oestrogen and testosterone
It decreases LH and FSH and oestrogen and testosterone
it decreases fertility an increases hypothalamic amenorrhoea
what is the evidence of metabolism and reproduction
OB Ob mouse was hyperphagic and obese
- had low gonads
- infertile
- didn’t mature sexually
what happened to gonads and weight when obob mouse was given Leptin
(+puberty and fertility)
Reduced obesity
restore GN secretion
induce puberty
restore fertility
what is amenorrhoea
an abnormal absence of menstruation.
is amenorrhoea due to the hypothalamus
if so why
yes
Sometimes the hypothalamus stops producing GnRH, which, in turn, will reduce the amount of other hormones produced (FSH, LH, and estrogen). Ovulation and menstruation stop, resulting in infertility.
what is kisspeptin
A GnRH secretagogue
what does kisspeptin neurons do
KISS1 neurons highly responsive to oestrogen, implicated in both + and – central feedback of sex steroids on GnRH production
Metabolic influences on reproduction mediated by leptin via the kisspeptin system
Puberty
Reproduction
what does leptin do to kisspeptin
Leptin promotes GnRH function via an indirect action on forebrain neurons. We tested whether leptin deficiency or leptin resistance due to a high-fat diet (HFD) can regulate the potent reproductive neuropeptide kisspeptin.
what does starvation do to the GH/IGF axis
GH resistance
increased GH and a decrease in IGF-I
due to
downregulation of hepatic GH receptor
is the effect of GH/IGF axis reversible
yes with re-feeding
what does starvation do to cortisol levels
Pulsatile Rhythm
what does starvation do to thyroid biomarker levels
It decreases TSH and T4
leading to less conversion to T3 but more to rT3 (inactive form)
consequences of starvation on thyroid gland
- Lower basal metabolic rate
- Conserve energy
