The somatopause. What stops our growth and diminishes GH secretion?

Transcription

1 The somatopause What stops our growth and diminishes GH secretion?

2 What extends or stops statural growth? Statural growth is extended if the early growth rate is slowed underfed adolescents grow for a longer time until they attain a critical body mass Growth is stopped when a critical body mass is attained

3 What stops or extends statural growth? Statural growth is stopped by a brain mechanism that inhibits secretion of hormones of growth When this inhibitory mechanism is blocked, rapid statural growth is reinstated Tissues must remain competent to grow

4 What stops or extends statural growth? Mature animals stop growing (lower line) Rapid growth is reinstated when limbic forebrain is separated from the hypothalamus Tissues here had retained the capacity to grow

5 Brain controls of GH secretion Somatostatin inhibits GHRH stimulates GH secretion IGF-I negative feedback

6 What else stops statural growth? Loss of capacity to respond to hormones of growth ( in the bone growth zone) At puberty, sex hormones (estrogen) close the epiphyseal growth zones in humans

7 Can exercise affect statural growth? Exercise changes a non-growing hamster into a rapidlygrowing one Abundant nutrition needed Increased GH needed

8 Can exercise affect statural growth? Skeletal elongation during 4 weeks of running

9 Exercise-induced weight gain is due to whole-body growth Growth of all parts of the skeleton is accelerated by exercise

10 Nutritional control of statural growth GH can stimulate transcription of growth factors when nutrients are abundant Under negative energy balance, insulin and growth factor levels are low

11 What causes acceleration of growth in exercising hamsters? Doubling of: GH pulses GH amplitudes

12 Can exercise stimulate statural growth? At least in one animal model, it does Acceleration of growth occurs through stimulation of pulsatile GH secretion Exercise appears to act on the neuroendocrine clock that regulates GH secretion

13 Can exercise stimulate statural growth in humans? Endurance exercise can act as energy drain and stunt instead of accelerating growth Endurance exercise can stimulate pulsatile GH secretion

14 Can exercise increase GH pulsatility in humans? Yes, in 32-y old women variable training intensity Increased GH pulse amplitude and daily secretion at high intensity

15 Can exercise increase GH pulsatility in humans? Yes, in postmenopausal women variable training intensity Increased GH pulse frequency and amplitude at high intensity

16 What regulates reparative growth? The same mechanism as in statural growth with anabolic hormone secretion turned down to a low rate Depends on adequate nutrition adequate stimulation by hormones of growth

17 What regulates reparative growth? Adequate stimulation of hormones of growth Exercise intensity type Specific nutrients

18 What is hypertrophic growth? Expression of genes for structural proteins and growth factors within the stimulated tissue Usually measured as increased mrna production

19 What controls hypertrophic growth? Mechanical loading of musculo-skeletal system Low dependence on nutrition Low dependence on hormones of growth

20 GH is not necessary for hypertrophic growth (body building) Hypox rats Food-restricted rats. Both exhibit muscle hypertrophy increased expression of IFG-I genes

21 Does GH administration increase hypertrophic growth? GH abuse in athletics No selective increase in muscle mass No increase in muscle strength Increase in lean body mass as a whole Water retention Insulin resistance

22 What is the function of GH in hypertrophic growth? If GH is not necessary for hypertrophic growth, what is the function of exerciseinduced GH secretion? Stimulation of IGF-I secretion Lipolysis and lipid utilization Increased plasma glucose

23 What is the function of exercise-induced GH surges? Metabolic? glucose lipids Reparative? protein synthesis in muscle bone conn.tissue

24 Is growth programmed or is it determined by the environment? Timing of statural growth is preprogrammed but can be changed by exercise plane of nutrition Hypertrophic growth persists through the life span Reparative growth declines with age

25 Change in pulsatile GH secretion with age Pulsatile GH secretion is highest during the prepubertal growth spurt Pulsatile GH secretion declines as we age

26 Statural or incremental growth in early rapid growth slower growth during childhood growth acceleration around puberty cessation of growth humans

27 Change in total GH secretion with age 24-h GH concentration is highest during prepubertal growth spurt Total GH secretion declines as we age

28 Somatopause Exponential decline in GH secretion ( somatopause ) GH levels declines by 50% every 7 years

29 Somatopause The amount of visceral body fat is inversely related to GH secretion

30 Impact of somatopause 30 to 50% loss of lean body mass 1 to 3%/year decline in bone mineral density 10 to 50% increase in body fat (especially visceral fat) sleep disturbance reduced immune function

31 Is somatopause primary or secondary? Could age-associated declines in physical activity contribute? There is a general decline in the volume of physical activity with age

32 Could accumulation of (visceral) fat contribute to GH decline? There is a progressive loss of lean body mass with age There is a progressive increase in body fat content with age

33 Is change in body composition primary or secondary? Exponential decline in GH secretion ( somatopause ) with increasing levels of body fat

34 Are aging changes in body composition due to changes in GH secretion? GH injections in 70- year old men increase LBM decrease body fat

35 Causes of somatopause: decreased estradiol secretion? Estradiol slows down age-associated GH decline

36 Causes of somatopause: decreased testosterone secretion? GH secretion is directly proportional to testosterone

37 Other possible causes/consequences of somatopause disordered sleep reduced IGF-I secretion (and reparative growth) more disorderly and less pulsatile GH secretion

38 Some determinants of reduced reparative growth with aging more disorderly GH secretion sex hormone withdrawal IGF-I withdrawal fragmentation of sleep obesity

39 How dose exercise increase GH pulsatility in old humans? Before training After 30 weeks of training