Still only reading the abstracts due to lack of access.
This issue is a continuation on the growth hormone papers from last issue. There is a lot more mentions of ghrelin in these papers than in the ones I read from 1999. It's one of the secretagogues.
"Relationship Between Exercise and Growth Hormone Neuroendocrine Function". A review of the effects of exercise on growth hormone. This one could be interesting.
"Cellular and Molecular Mechanisms of Growth Hormone Action on Skeletal Muscle: Implications for Treatment of Age-Associated Sarcopenia". How growth hormone/IGF-1 make muscles grow.
"Assessing Safety and Efficacy of Growth Hormone Replacement in Aging by Community Physicians". Review on safety profile I think.
"Growth Hormone: Challenges and Opportunities for the Biotechnology Sector". Some kind of review. Dunno.
"Localization and the Role of Growth Hormone Secretagogues in the Central Nervous System". Which bits of the brain the secretagogues touch.
"Growing Pains: Bioethical Perspectives on Growth Hormone Replacement Research". Ethics.
"Sex-Steroid Hormone Modulation of the Tripeptidyl Control of the Human Somatotropic Axis". I think it's on estrogen modulation of GH. Maybe testosterone too.
"N6-Furfuryladenine (Kinetin) as a Potential Anti-Aging Molecule". Something completely different. A cell-division inducer being touted as an anti-oxidant. Not growth hormone related, but doesn't sound like much fun either.
Book review of the 5th edition of the Handbook of the Biology of Aging. Supposedly good.
The usual literature review section reviewing a paper about alternative splicings of human telomerase reverse transcriptase, and possible control mechanisms of telomerase through control of splicing enzymes.
Showing posts with label growth hormone. Show all posts
Showing posts with label growth hormone. Show all posts
Tuesday, January 17, 2012
Monday, January 16, 2012
December 2001, sourceless.
Continuing the cheating. Only have abstracts available and I'm mostly happy about that, since it's an issue on growth hormone and I've had enough of that particular topic.
"Issues Regarding the Routine and Long-Term Use of Growth Hormone in Anti-Aging Medicine". Probably what it says in the title.
"A Word of Caution: Can Growth Hormone Accelerate Aging?". Creator of the GH receptor knock-out mice warning that growth hormone is maybe not great.
"Age-Related Decreases in Growth Hormone and Insulin-Like Growth Factor (IGF)–1: Implications for Brain Aging". Growth hormone and the brain, and why the knock-out mice are not relevant maybe.
"Growth Hormone Releasing Hormone Treatment in Normal Aging". 6 month study injecting growth hormone releasing hormone into old people. Lean body mass increase, abdominal fat decrease (5-8%), maybe improved cognition, no better sleep. Didn't work for women under estrogen supplementation.
"Natural and Synthetic Growth Hormone Secretagogues: Endocrine and Nonendocrine Activities Suggesting Their Potential Usefulness as Anti-Aging Drug Interventions". On the non-growth-hormonal effects of growth hormone secretagogues.
"Hormone Modulation, Low Glycemic Nutrition, and Exercise Instruction: Effects on Disease Risk and Quality of Life". Results of looking at 100 people on growth hormone, DHEA, testosterone, estrogen and progesterone supplementation.
"Growth Hormone Excess and Cancer". Does it make it more likely.
After that barrage, there is a short report on the second SENS roundtable, too short to have any details.
Finally, the usual literature review, looking at telomerase ectopically expressed in heart cells of mice. It inhibited apoptosis after heart attacks, and decreased affected area by 23%. Made the hearts bigger too.
"Issues Regarding the Routine and Long-Term Use of Growth Hormone in Anti-Aging Medicine". Probably what it says in the title.
"A Word of Caution: Can Growth Hormone Accelerate Aging?". Creator of the GH receptor knock-out mice warning that growth hormone is maybe not great.
"Age-Related Decreases in Growth Hormone and Insulin-Like Growth Factor (IGF)–1: Implications for Brain Aging". Growth hormone and the brain, and why the knock-out mice are not relevant maybe.
"Growth Hormone Releasing Hormone Treatment in Normal Aging". 6 month study injecting growth hormone releasing hormone into old people. Lean body mass increase, abdominal fat decrease (5-8%), maybe improved cognition, no better sleep. Didn't work for women under estrogen supplementation.
"Natural and Synthetic Growth Hormone Secretagogues: Endocrine and Nonendocrine Activities Suggesting Their Potential Usefulness as Anti-Aging Drug Interventions". On the non-growth-hormonal effects of growth hormone secretagogues.
"Hormone Modulation, Low Glycemic Nutrition, and Exercise Instruction: Effects on Disease Risk and Quality of Life". Results of looking at 100 people on growth hormone, DHEA, testosterone, estrogen and progesterone supplementation.
"Growth Hormone Excess and Cancer". Does it make it more likely.
After that barrage, there is a short report on the second SENS roundtable, too short to have any details.
Finally, the usual literature review, looking at telomerase ectopically expressed in heart cells of mice. It inhibited apoptosis after heart attacks, and decreased affected area by 23%. Made the hearts bigger too.
Sunday, July 17, 2011
Predictors of Growth Hormone Secretion in Aging
Summary: Growth hormone again
Interestingness: 2
Paper by Mark L Hartman, Jody L Clasey, Arthur Weltman and Michael O Thorner in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.
(((
Growth hormone (GH) secretion goes down with age at an inversely logarithmic rate. It is almost down all the way by time we are in our 30s. This may not be due to age alone though, since there are high correlations between integrated GH concentration and each of BMI, percentage body fat and fitness, as measured by oxygen consumption, especially in men (in women the effect does not reach the magic 0.05).
Most of the reasons listed for the decrease we've seen before already (growth hormone papers). Some that I haven't:
In their own studies, they find correlations between integrated GH concentration and each of abdominal visceral fat, fasting insulin and IGF-1, independent of age, sex, total body fat mass, percentage fat, 24 hour mean estradiol and testosterone, and peak oxygen uptake, in a group of 40 people in their 20s and 62 in the 57-80 year old range. Also, a high correlation between the combination of age and sex with IGF-1.
)))
Abstract follows:
Interestingness: 2
Paper by Mark L Hartman, Jody L Clasey, Arthur Weltman and Michael O Thorner in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.
(((
Growth hormone (GH) secretion goes down with age at an inversely logarithmic rate. It is almost down all the way by time we are in our 30s. This may not be due to age alone though, since there are high correlations between integrated GH concentration and each of BMI, percentage body fat and fitness, as measured by oxygen consumption, especially in men (in women the effect does not reach the magic 0.05).
Most of the reasons listed for the decrease we've seen before already (growth hormone papers). Some that I haven't:
- GH secretions four times higher during stage 3 and 4 sleep. Deep sleep goes to the shit with age.
- Possible path by which high fat reduces GH: high free insulin-like growth factor 1 (IGF-1). But then they quote study showing inverse correlation between free IGF-1 and visceral fat.
In their own studies, they find correlations between integrated GH concentration and each of abdominal visceral fat, fasting insulin and IGF-1, independent of age, sex, total body fat mass, percentage fat, 24 hour mean estradiol and testosterone, and peak oxygen uptake, in a group of 40 people in their 20s and 62 in the 57-80 year old range. Also, a high correlation between the combination of age and sex with IGF-1.
)))
Abstract follows:
Growth hormone (GH) secretion decreases progressively after mid-puberty in both men and women. This decrease occurs predominantly before age 40-50 and affects both daytime and nocturnal GH secretion. A reduction in the amplitude of GH secretory pulses accounts for the majority of the reduction in GH secretion. With aging, changes in hypothalamic function may occur that result in decreased GH secretion. These changes may include decreased secretion of GH-releasing hormone and/or the putative natural ligand for the GH secretagogue receptor or an increase in somatostatin release. Multiple physiological factors have been reported to regulate GH secretion including sleep, body composition (% body fat and amount of abdominal visceral fat), aerobic physical fitness and serum concentrations of insulin-like growth factor-I (IGF-I), gonadal steroids and insulin. Changes in these factors with aging may contribute to the reduction in GH secretion observed in older adults. However, these physiological predictors of GH secretion are not independent of one another and the relative importance of these factors in the regulation of GH secretion is not known. Preliminary evidence suggests that the amount of abdominal visceral fat and fasting serum concentrations of insulin and IGF-I are the most important predictors of 24-hour GH release in healthy adults, independent of age and gender. Bi-directional feedback between these three factors and GH secretion may account for the strong relationships observed.
Sunday, July 3, 2011
Network-Like Facets of Neuroendocrine Aging in the Human: Specific Disruption of Feedback and Feedforward Linkages Within the Aging Somatotropic ...
Full title, since it didn't fit: Network-Like Facets of Neuroendocrine Aging in the Human: Specific Disruption of Feedback and Feedforward Linkages Within the Aging Somatotropic, Gonadotropic, and Corticotropic Axes in Men and Women
Summary: Lots of facts about growth hormone, leutinising hormone, follicle-stimulating hormone and gonadotropin-releasing hormone, with very little cohesion.
Interestingness: 3
Paper by Johannes D Veldhuis in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.
(((
This is another long review paper by Veldhuis mainly about growth hormone (GH) and its friends, even though its supposedly about the interaction between different hormonal axes. It has 266 references. It's too much information to summarise. I'll jot some notes. A lot of the same information as in Veldhuis's previous paper is covered as well as in all the other GH papers. I'll skip bits that I think are repeated. A lot of the graphs presented don't look very convincing. They tend to have around 10 people per group, so the curves look like they could change easily.
Newer data says more GH secreted by women than men, and decline with aging is half as slow.
Secretion pulses more irregular and lower in older people for GH, leutinising hormone (LH), insulin and prolactin. Follicle-stimulating hormone (FSH) secretion pulse and base go up.
Intra-venous gonadotropin releasing hormone (GnRH) pulses normalised LH secretion in older men.
Inferenced mechanisms mentioned:
They do some computer models of the GnRH-LH-T axis and from those they like the following hypotheses for the loss of synchrony between LH and T release in older men:
)))
Abstract follows:
Summary: Lots of facts about growth hormone, leutinising hormone, follicle-stimulating hormone and gonadotropin-releasing hormone, with very little cohesion.
Interestingness: 3
Paper by Johannes D Veldhuis in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.
(((
This is another long review paper by Veldhuis mainly about growth hormone (GH) and its friends, even though its supposedly about the interaction between different hormonal axes. It has 266 references. It's too much information to summarise. I'll jot some notes. A lot of the same information as in Veldhuis's previous paper is covered as well as in all the other GH papers. I'll skip bits that I think are repeated. A lot of the graphs presented don't look very convincing. They tend to have around 10 people per group, so the curves look like they could change easily.
Newer data says more GH secreted by women than men, and decline with aging is half as slow.
Secretion pulses more irregular and lower in older people for GH, leutinising hormone (LH), insulin and prolactin. Follicle-stimulating hormone (FSH) secretion pulse and base go up.
Intra-venous gonadotropin releasing hormone (GnRH) pulses normalised LH secretion in older men.
Inferenced mechanisms mentioned:
- Lower endogenous growth hormone-releasing hormone (GHRH) secretion and/or lower growth hormone releasing peptide (GHRP) effect could explain loss of GH secretory pulse.
- Evidence for too much somatostatin and GHRH deficiency. Neither alone enough.
- Partial GnRH deficiency and Leydig-cell steroidogenic defect both exist, and the latter is not fixed by external GnRH.
They do some computer models of the GnRH-LH-T axis and from those they like the following hypotheses for the loss of synchrony between LH and T release in older men:
- Lower feed-forward drive of T synthesis by Leydig cells.
- Same, plus lowered negative-feedback by T of GnRH and LH release.
)))
Abstract follows:
The present update highlights the impact of age on dynamic regulatory changes arising singly and multiply within several prototypical neuroendocrine axes in the human. A neuroendocrine axis is viewed here as a homeostatic unit maintained by multivalent interactions or network-like integration among CNS-hypothalamic, pituitary, and target-tissue sites; for example, the GHRH/somatostatin-GH-IGF-I, GnRH-LH-sex-steroid and CRH/AVP-ACTH-cortisol feedback-controlled axes. Homeostatic control is driven by (time-lagged) interglandular signaling and dose-sensitive interfaces. According to this broader perspective, a neuroendocrine system operates as an interdependent ensemble of reciprocally communicating control nodes. This dynamic precept provides a foundation for identifying among the earliest vivid features of signaling disruption within the somatotropic, gonadotropic, and corticotropic (as well as insulinotropic) axes in healthy aging men and women. Internodal linkages likely deteriorate further in the face of acute or chronic illness, medication use, systemic stress and/or hospitalization, resulting at times in overt failure of neuroglandular output. This extended concept offers a notion of neuroendocrine axis frailty as a precursor to frank endocrinesystem disability in aging. Such a framework also confers the expectation that pluri- or multiaxis disruption (e.g., combined somatotropic and gonadal) would further adversely impact homeostatic vigor in aging individuals.
Sunday, May 1, 2011
Endocrine Determinants of Successful Aging in the Male
Summary: A whole bunch of hormone levels go down when men get old
Interestingness: 3
Paper by Annewieke W van den Beld and Steven WJ Lamberts in the Journal of Anti-Aging Medicine, Volume 3, Issue 2, June 2000.
(((
This is another paper that reads like a review paper, even though they keep referring to their study of 400 73-94 year old men in the Netherlands. Most of what's quoted is about other studies. When they talk about their own study, I'll note it, and I'll mainly focus on their results, not the survey. Their study mostly lacks graphs and numbers, so I'll stick to what they describe it as (increase, decrease, etc).
They "confirm" other studies that say that muscle strength is the major feature that determines whether an old man remains functionally independent.
Mean serum total testosterone (T) in males goes down by about 30% between being 25 and 75. Mean serum free T goes down by 50%. The difference is explained by an increase in sex-hormone-binding globulin (SHBG). In their study they found a correlation between free T and muscle strength, but none between T and life satisfaction.
In their study they see luteinising hormone (LH), which triggers release of T by the testicles, going up with age, and it being inversely correlated with T concentrations. Other studies show mixed results for this relation.
Drop in estradiol (E2) and estrone (E1) with age. In their study, strong correlation between E2 and bone density, and E2 and life satisfaction.
Drop in dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) with age. DHEAS level at 85 is one fifth of level at 30. DHEAS levels in adults > 10 times higher than cortisol (!). In their study, no relation between DHEAS and muscle strength, and relation between DHEAS and bone density disappears when adjusting for T and E1,E2 levels.
And again growth hormone (GH) secretion drops with age, insulin-like growth factor 1 (IGF-1) drops with age, IGF-binding protein 3 (IGFBP-3) drops with age, but IGFBP-2 and IGFBP-1 increase with age. Their study concurs. Also in their study, they didn't see relation between IGF-1 and physical functional status, but did see a strong inverse relation between IGFBP-2 and muscle strength, and they like IGFBP-2 as an indicator of overall level of physical functional status.
)))
Abstract follows:
Interestingness: 3
Paper by Annewieke W van den Beld and Steven WJ Lamberts in the Journal of Anti-Aging Medicine, Volume 3, Issue 2, June 2000.
(((
This is another paper that reads like a review paper, even though they keep referring to their study of 400 73-94 year old men in the Netherlands. Most of what's quoted is about other studies. When they talk about their own study, I'll note it, and I'll mainly focus on their results, not the survey. Their study mostly lacks graphs and numbers, so I'll stick to what they describe it as (increase, decrease, etc).
They "confirm" other studies that say that muscle strength is the major feature that determines whether an old man remains functionally independent.
Mean serum total testosterone (T) in males goes down by about 30% between being 25 and 75. Mean serum free T goes down by 50%. The difference is explained by an increase in sex-hormone-binding globulin (SHBG). In their study they found a correlation between free T and muscle strength, but none between T and life satisfaction.
In their study they see luteinising hormone (LH), which triggers release of T by the testicles, going up with age, and it being inversely correlated with T concentrations. Other studies show mixed results for this relation.
Drop in estradiol (E2) and estrone (E1) with age. In their study, strong correlation between E2 and bone density, and E2 and life satisfaction.
Drop in dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) with age. DHEAS level at 85 is one fifth of level at 30. DHEAS levels in adults > 10 times higher than cortisol (!). In their study, no relation between DHEAS and muscle strength, and relation between DHEAS and bone density disappears when adjusting for T and E1,E2 levels.
And again growth hormone (GH) secretion drops with age, insulin-like growth factor 1 (IGF-1) drops with age, IGF-binding protein 3 (IGFBP-3) drops with age, but IGFBP-2 and IGFBP-1 increase with age. Their study concurs. Also in their study, they didn't see relation between IGF-1 and physical functional status, but did see a strong inverse relation between IGFBP-2 and muscle strength, and they like IGFBP-2 as an indicator of overall level of physical functional status.
)))
Abstract follows:
Frailty is characterized by generalized weakness, impaired mobility and balance, and poor endurance. Loss of muscle strength is an important factor in the process of frailty, and is the limiting factor for an individual's chances of living an independent life until death. In men, several hormonal systems show a decline in activity during aging. Serum bioavailable testosterone (T) and estradiol (E2), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), and growth hormone (GH) and insulin-like growth factor (IGF)-I concentrations all decrease during aging in men. Physical changes during aging have been considered physiological, but there is evidence that some of these changes are related to this decline in hormonal activity. Studies on hormone administration in the elderly appear to be promising. However, until now, hormone replacement is not yet proven to beneficial and safe.
Wednesday, April 27, 2011
GH Secretagogues in Aging
Summary: Growth hormone secretagogues bind all over the place. Not much to recommend them.
Interestingness: 2
Paper by Emanuela Arvat, Roberta Giordano, Fabio Broglio, Laura Gianotti, Lidia Di Vito, Gianni Bisi, Andrea Graziani, Mauro Papotti, Giampiero Muccioli, Romano Deghenghi and Ezio Ghigo in the Journal of Anti-Aging Medicine, Volume 3, Issue 2, June 2000.
(((
This covers similar ground to the other papers on growth hormone that I've summarised before (http://readingrejuvenationresearch.blogspot.com/search/label/growth hormone) but talks only about the synthetic compounds. I think all the studies it mentions are very small (around 20-30 people). This is an eighth-assed attempt at a summary.
The GHS are treated as a group but it seems like there's a lot of differences between them which I won't summarise. The method of inducing growth hormone (GH) release seems to be as a somatostatin (SS) antagonist. The GH stimulation effect is high in puberty and adults, but not on old people. Hypothalamic receptors were lower in middle aged and old people, than in young adults.
Some studies show increase in GH, insulin-like growth factors (IGF) I and II, and IGF binding protein 3 (IGFBP3) in old people when given specific GHSes, others increase in fat-free mass and energy expenditure in obese people, others no change in fat or lean mass in elderly. All of these are shortish (2-month), small studies.
Also reported on non-GH effects of GHS, like release of prolactin (PRL) and adrenocorticotropic hormone (ACTH), and bindings all over the cardiovascular system, with maybe some anti-apoptotic effect.
)))
Abstract follows:
Interestingness: 2
Paper by Emanuela Arvat, Roberta Giordano, Fabio Broglio, Laura Gianotti, Lidia Di Vito, Gianni Bisi, Andrea Graziani, Mauro Papotti, Giampiero Muccioli, Romano Deghenghi and Ezio Ghigo in the Journal of Anti-Aging Medicine, Volume 3, Issue 2, June 2000.
(((
This covers similar ground to the other papers on growth hormone that I've summarised before (http://readingrejuvenationresearch.blogspot.com/search/label/growth hormone) but talks only about the synthetic compounds. I think all the studies it mentions are very small (around 20-30 people). This is an eighth-assed attempt at a summary.
The GHS are treated as a group but it seems like there's a lot of differences between them which I won't summarise. The method of inducing growth hormone (GH) release seems to be as a somatostatin (SS) antagonist. The GH stimulation effect is high in puberty and adults, but not on old people. Hypothalamic receptors were lower in middle aged and old people, than in young adults.
Some studies show increase in GH, insulin-like growth factors (IGF) I and II, and IGF binding protein 3 (IGFBP3) in old people when given specific GHSes, others increase in fat-free mass and energy expenditure in obese people, others no change in fat or lean mass in elderly. All of these are shortish (2-month), small studies.
Also reported on non-GH effects of GHS, like release of prolactin (PRL) and adrenocorticotropic hormone (ACTH), and bindings all over the cardiovascular system, with maybe some anti-apoptotic effect.
)))
Abstract follows:
Growth hormone (GH) secretagogues (GHS) are synthetic peptidyl and nonpeptidyl molecules which possess strong, dose-dependent and reproducible GH-releasing activity, even after oral administration. GHS release GH via actions on specific receptors at the pituitary and, mainly, at the hypothalamic level. GHS likely act as functional SS antagonists and meantime enhance the activity of growth hormone-releasing hormone (GHRH)-secreting neurons. In fact, GHS need the integrity of hypothalamus-pituitary unit to fully show their GH-releasing effect. The GH-releasing effect of GHS is reduced in aging likely reflecting concomitant GHRH hypoactivity and somatostatinergic hyperactivity, though impaired activity of the putative GHS-like ligand and/or receptors has also to be taken into account. Orally active GHS have been proposed as rejuvenating anabolic treatment of somatopause (age-related changes in metabolism, structure functions, and body composition partially reflecting the aging of GH/IGF-I axis). No definitive evidence of their clinical usefulness as anabolic agents has been provided yet. On the other hand, GHS have specific receptors in other central and peripheral endocrine and nonendocrine tissues. These receptor subtypes mediate GH-independent biological activities linked to the neuro-endocrinology of aging. For instance, GHS: (a) possess adrenocorticotropic hormone (ACTH)-releasing activity, which is increased in elderly subjects; (b) influence sleep pattern rejuvenating it in elderly subjects; (c) stimulate food intake; (d) have cardiovascular activities including protection against cardiac ischemia and cardiomyocyte apoptosis as well as increase in cardiac contractility. These "other than GH" central and peripheral activities are now carefully under evaluation.
Saturday, March 20, 2010
Effectiveness of Growth Hormone (GH) Secretagogues in Diagnosing and Treating GH Secretory Deficiency in Aging Men
Summary: Growth hormone releasing peptide (GHRP) increases effect of growth hormone releasing hormone on inducing growth hormone release, even when not given immediately prior. GHRP probably blocks somatostatin. Levels of GHRP's natural equivalent probably drop during aging.
Interestingness: 1
Paper by Richard F Walker and Barry B Bercu in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.
(((Yet another growth hormone paper. This one at least is neatly done, sticking to only one specific issue and comes with an easy conclusion)))
(((In this study, the older group is a bunch of people between 37 and 68, the younger group is between 16 and 21. The results seem to only refer to the male subsets. These groups are tiny, with six people in some, and three in others)))
Old people release way less growth hormone (GH) than young people when given GH releasing hormone (GHRH), but they release about the same GH when given GH releasing peptide (GHRP) (((an artificial peptide found to release GH, not found yet in the body naturally))) in older as in younger people. The amount released due to GHRP is much higher than that produced when GHRH alone is given. The relative effect of GHRP is much higher in older people: young people released 1.5 times as much GH when given GHRP compared to GHRH, but older people released 20.5 times as much when given GHRP compared to GHRH. When given less GHRP, less GH is released (((this is part of what they want to show, making the connection that older people probably have lower levels of GHRP or equivalent))).
GHRP only enhances the effect of the present GHRH though. If GHRH receptors are blocked with antagonists, GHRP doses don't lead to increased GH release. Giving GHRH and GHRP combined also leads to greater release than the sum of the releases when given separately. This is consistent with GHRP acting as a functional blocker of somatostatin.
Giving older people GHRP for 10 days, and then giving them GHRH the day after, released much more GH than without the 10 days of preparation. Since GHRP is metabolysed in minutes, this means that GHRP is not just acting directly ((("GHRH signal transduction" is what the paper calls it))) (((the increases in these priming examples are much lower than the immediately-prior dosing though)))
Abstract follows:
Interestingness: 1
Paper by Richard F Walker and Barry B Bercu in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.
(((Yet another growth hormone paper. This one at least is neatly done, sticking to only one specific issue and comes with an easy conclusion)))
(((In this study, the older group is a bunch of people between 37 and 68, the younger group is between 16 and 21. The results seem to only refer to the male subsets. These groups are tiny, with six people in some, and three in others)))
Old people release way less growth hormone (GH) than young people when given GH releasing hormone (GHRH), but they release about the same GH when given GH releasing peptide (GHRP) (((an artificial peptide found to release GH, not found yet in the body naturally))) in older as in younger people. The amount released due to GHRP is much higher than that produced when GHRH alone is given. The relative effect of GHRP is much higher in older people: young people released 1.5 times as much GH when given GHRP compared to GHRH, but older people released 20.5 times as much when given GHRP compared to GHRH. When given less GHRP, less GH is released (((this is part of what they want to show, making the connection that older people probably have lower levels of GHRP or equivalent))).
GHRP only enhances the effect of the present GHRH though. If GHRH receptors are blocked with antagonists, GHRP doses don't lead to increased GH release. Giving GHRH and GHRP combined also leads to greater release than the sum of the releases when given separately. This is consistent with GHRP acting as a functional blocker of somatostatin.
Giving older people GHRP for 10 days, and then giving them GHRH the day after, released much more GH than without the 10 days of preparation. Since GHRP is metabolysed in minutes, this means that GHRP is not just acting directly ((("GHRH signal transduction" is what the paper calls it))) (((the increases in these priming examples are much lower than the immediately-prior dosing though)))
Abstract follows:
This study was conducted primarily to determine the utility of recombinant growth hormone releasing hormone (GHRH) and xenobiotic GH-releasing peptide (GHRP) administered sequentially or in combination, as diagnostic agents for pituitary-based, GH secretory dysfunction in aging men. The secondary purpose was to test the hypothesis that loss of sensitivity to stimulation with GHRH during aging results, at least in part, from reduced exposure of the pituitary gland to the yet unknown, endogenous compound whose activity is stimulated by GHRP. Increases in serum GH following GHRH administration were significantly lower in older men than they were in adolescent and young adult men. In contrast, changes in serum GH following GHRP were comparable in the younger and older men. Because robust GH secretion in response to administration of exogenous GHRH or GHRP is interpreted as representing adequate concentrations of complementary endogenous GHRP and GHRH, respectively, the data suggested that older subjects were deficient in endogenous GHRP. Accordingly, it was of interest to determine whether priming with GHRP would restore the response to GHRH in these men. Ten consecutive days of priming with GHRP caused the responses to GHRH challenge to be significantly improved compared with responses observed before priming. GH secretion following co-administration of GHRH and GHRP were comparable in both age groups. The results of this study suggest that functional elements of pituitary somatotrophs directly related to expression of GHRH activity are intact during aging, but lose their effectiveness in part because of complementary secretagogue (endogenous GHRP analogy) deficiencies. Whereas priming with GHRP demonstrates the plasticity of GHRH signal transduction mechanisms in aging men, the data do not allow determination of whether GHRH or GHRP receptors or second messengers for either or both of these secretagogues become down-regulated. Future studies are designed to make these determinations and to further investigate and confirm the validaity of using GH scretagogues to reactivate the GH axis in the elderly.
Monday, March 8, 2010
Use of Growth Hormone for Treatment of Anatomic and Physiologic Decrements Associated with Aging
Summary: Effects of growth hormone on cardiovascular health and its periphery. Not much there.
Interestingness: 1
Paper by Bengt-Åke Bengtsson, Gudmundur Johannsson, and Jörgen Isgaard, all of them MD, PhD, in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.
Case studies show improvements in heart function in heart failure patients when given growth hormone (GH). Placebo-controlled studies fail to replicate those effects. In rats, insulin-like growth factor 1 (IGF-1) lowers heart cell apopstosis after induced heart attacks.
Like in the previous paper summarised, they note the similarities between GH deficiency and Syndrome X (insulin resistance plus hypertension) (abdomen/visceral obesity, insulin resistance, high triglycerides, low levels of high density lipoprotein (HDL), hypertension, high plasma fibrinogen, high plasminogen activator inhibitor (PAI-1) activity, premature atherosclerosis and high cardiovascular disease mortality), and also the association between higher abdominal/visceral fat and lower secretions of GH and subsequent IGF-1. In some trials, massive weight loss restores normal levels of GH secretion, but in others it doesn't.
In GH-deficient people, GH supplementation does lots of good things (lower visceral fat, lower diastolic blod pressure, total cholesterol, and low density lipoprotein (LDL), and raises HDL).
In GH sufficient people, it doesn't help the obese lose weight, but in a nine-month study by the authors on obese men, it lowered total body fat, abdominal fat, total cholesterol, triglycerides, it improved insulin sensitivity and lowered diastolic blood pressure, but plasma fibrinogen levels increased. Hypothesis given for the effects are:
Concludes with a section about end-stage renal failure patients and a 6-month study by the authors showing increased muscle mass and strength, and increased albumin concentration in these patients when given a low dose of GH.
Abstract follows:
Interestingness: 1
Paper by Bengt-Åke Bengtsson, Gudmundur Johannsson, and Jörgen Isgaard, all of them MD, PhD, in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.
Case studies show improvements in heart function in heart failure patients when given growth hormone (GH). Placebo-controlled studies fail to replicate those effects. In rats, insulin-like growth factor 1 (IGF-1) lowers heart cell apopstosis after induced heart attacks.
Like in the previous paper summarised, they note the similarities between GH deficiency and Syndrome X (insulin resistance plus hypertension) (abdomen/visceral obesity, insulin resistance, high triglycerides, low levels of high density lipoprotein (HDL), hypertension, high plasma fibrinogen, high plasminogen activator inhibitor (PAI-1) activity, premature atherosclerosis and high cardiovascular disease mortality), and also the association between higher abdominal/visceral fat and lower secretions of GH and subsequent IGF-1. In some trials, massive weight loss restores normal levels of GH secretion, but in others it doesn't.
In GH-deficient people, GH supplementation does lots of good things (lower visceral fat, lower diastolic blod pressure, total cholesterol, and low density lipoprotein (LDL), and raises HDL).
In GH sufficient people, it doesn't help the obese lose weight, but in a nine-month study by the authors on obese men, it lowered total body fat, abdominal fat, total cholesterol, triglycerides, it improved insulin sensitivity and lowered diastolic blood pressure, but plasma fibrinogen levels increased. Hypothesis given for the effects are:
- Higher insulin sensitivity: lower fatty-acid exposure by the liver through lower abdominal fat. Or increased glucose transport by the skeletal muscles
- Lower total cholesterol: more liver LDL-receptors
- Lower triglycerides: increased insulin-stimulated glucose uptake
- Lower diastolic blood pressure: reduced peripheral vascular resistance through increased insulin-sensitivity or through IGF-1 action on the vascular wall with increased levels of nitric oxide.
Concludes with a section about end-stage renal failure patients and a 6-month study by the authors showing increased muscle mass and strength, and increased albumin concentration in these patients when given a low dose of GH.
Abstract follows:
There are striking similarities between Syndrome X or "the metabolic syndrome" and untreated GH deficiency in adults. The most central findings in both these syndromes are abdominal/visceral obesity and insulin resistance. Other features common to both syndromes are lipid abnormalities, increased prevalence of hypertension, elevated levels of plasma fibrinogen and plasminogen activator inhibitor (PAI)-l activity, premature atherosclerosis, and increased mortality from cardiovascular disease. GH treatment can improve several of the aberrations that GH deficiency has in common with Syndrome X. Recently, we have shown that nine months of treatment in a randomized, double-blind, placebo-controlled trial in middle-aged men with abdominal/visceral obesity reduced their total body fat and resulted in specific and marked decrease in both abdominal subcutaneous and visceral adipose tissue. Moreover, insulin sensitivity and lipoprotein profile improved, and diastolic blood pressure decreased.
A number of experimental and clinical studies suggest a potential role for GH as an addition to conventional therapy for the treatment of congestive heart failure (CHF). Recently, patients with heart failure due to idiopathic dilated cardiomyopathy showed a positive response to GH addition. However, so far, no placebo-controlled study with GH addition to standard optimal therapy in patients with CHF has been able to confirm these findings. Elderly patients on chronic hemodialysis are in a chronic catabolic phase with low lean body mass. We have recently performed a randomized double-blind placebo-controlled trial with GH in elderly on chronic dialysis. Six months of treatment improved lean body mass, muscle strength and walking capacity.
Monday, March 1, 2010
Neuroregulatory Pathophysiology of Impoverished Growth Hormone (GH) Secretion in the Aging Human
Summary: Review of possible regulatory causes of the decrease in growth hormone with age. I don't know if it comes to any conclusion, but it seems to suggest that there is too much somatostatin being secreted and either too little growth hormone releasing hormone or some other hypothetical growth hormone releasing peptide.
Interestingness: 2
Paper by JD Veldhuis in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.
(((This issue seems to consist mostly of the papers from the conference on endocrine and molecular interventions in aging reported on in the previous issue. Could get heavy)))
(((First repeat subject: growth hormone. Not one I find particularly interesting)))
Giving growth hormone (GH) to people with GH deficiency helps with many of their problematic psychological symptoms (reduced energy and sense of well-being, social isolation, depressed mood and increased anxiety) and physical symptoms (reduction in lean body mass, bone mineral density, basal metabolic rate, strength, glomerular filtration rate (((kidneys))), increase in body fat and cholesterol). Old people share many of the same problems. Maybe GH would be good for them too. (((The underlying drive in the paper is that increasing growth hormone would be a good thing. Considering the correlation between GH and IGF-1, and it and shortened lifespan, I think the assumption nowadays would be the opposite))). There are some side effects with GH supplementation (fluid retention, myalgia (((muscle pain))), arthralgia (((joint pain))), carpal tunnel syndrome, gynecomastia (((man-boobs))), glucose intolerance) but maybe by triggering it with growth hormone releasing hormone (GHRH) or growth hormone releasing peptides (GHRP) to secrete in its usual pulse-like manner the side-effects can be reduced or eliminated (((as in the previous GH post)))
GH secretion goes down by 50% every seven years in healthy men after hitting 20 years of age (((That's quite a different number from the 14% every decade cited in the previous paper. The graph shown purportedly showing that decline has 21 data points, a line of best fit that looks like it's not going down by half every 7 years after age 35. It also looks like if you were to take the 6 data points of men under 30 out, you'd be left with a horizontal line of best fit))). In pre-menopausal women, the rate of decline is half as fast but it becomes the same as men's after menopause. It is also lower to begin with (((The graph showing young male and female declines of total GH concentration (it integrates concentration over 24 hours) also seems remarkably dodgy for women. Taking out one outlier out of the 32 data points would seem to make it almost flat. Also, these declines are modeled as linear, which doesn't merge with the exponential declines in secretion. I think I'm missing something in the difference between secretion amounts and total concentrations))). The reason for the difference between the sexes is unknown but probably related to estradiol stimulating GH production.
There's also an exponentially declining link between BMI and GH, with a 1.5 kg/m^2 increase leading to a halving of secretion. (((Accompanying dodgy graph, but this one seems reasonable, except for what seems to me to be too little data to be doing exponential regression))) (((Personal hypohypothesis aside: could this be related to why higher BMI doesn't lead to higher mortality even in the presence of the high heart disease risk?))). This interacts with the age link since there's an increase in BMI with age as well. Abdominal fat also dampens the normally strong link between testosterone serum levels and GH secretion, although this dampening isn't as strong in women. The action of testosterone also seems to be by conversion to estradiol.
There are other covariates with age that might influence GH secretion such as fitness, disturbed sleep, different diet, medication, and illness. Little is known about these to be able to differentiate among causes of decline.
I'll skip for a bit to the model of influences presented later since it helps. The model suggested involves a lot of negative feedback loops to stop GH and IGF-1 from being too high. So GH induces IGF-1 which switches GH off. GHRH induces GH secretion, so both GH and IGF-1 turn GHRH off. Somatostatin turns off GH and GHRH secretion so GHRH, GH and IGF-1 all raise somatostatin secretion. Then there are substances that act on GHRH and somatostatin separately. GHRH is raised by GABA-B, galanin, alpha2-adrenergic and the suggested GHRP. Somatostatin is raised by B-2 adrenergic, but lowered by dopamine, serotonin (1-D), L-arginine, muscarinic cholinergic neurotransmission, and the imagined GHRP.
(((The backing of the above confuses me a bit, and is really not very useful, but here it goes))) Pyridostigmine, a cholinergic agonist, given over two days doubles the daily GH secretions by increasing the amount secreted in the pulse, not by increasing rate of pulsing. This link is attenuated with increased body fat. The equivalent of pyridostigmine in sheep stimulates GHRH and triggers a large GH secretions. The paper then suggests that pyridostigmine limits somatostatin, and that this suggests that the reduction in GH with age is due to both an increase in somatostatin and a lack of GHRH.
Alpha-2 adrenergic agonists increase GH in lots of mammals, including the human, partly by increasing GHRH secretion, and possibly by reducing somatostatin. Clonidine, an alpha-2 adrenergic agonist, is a weak GH inducer in humans though. Beta-2 adrenergic agonists lower GH production, and that's believed to be through somatostatin because they lower GH even in the presence of GHRH.
Dopamine is also a GH secretion inducer, but not much is known about how it changes with aging or across sexes. Also, serotoninergic (5-HT) stimulate GH by reducing somatostatin. Galanin also, being more effective in women than in men and the effect decreasing with age. Same with GABA-B, which works better in older women than in men. Corticotropin releasing hormone, leptin and neuropeptide Y are also mentioned as requiring more study (((but I assume they are also inducers of GH secretion)))
(((Back to the main thread))) Most external drivers of higher GH secretion are dampened with age, including GHRH, GHRP, opiates, GABA agonists, fasting, galanin, sleep, exercise,pyridostigmine, L-arginine, clonidine and L-dopa, but some are not, eg insulin-induced hypoglycemia, and combining L-arginine and GHRH or GHRP. This is consistent with somatostatin excess being one of the main culprits in the decline of GH with age since L-arginine hammers somatostatin. But since L-arginine alone doesn't restore the levels of GH fully, too much somatostatin is probably not the only cause, and there is likely a shortfall in GHRH and/or GHRP as well. Combinations of GHRH, synthetic ligands for the GHRP receptor and L-arginine are very effective at raising GH and IGF-1 secretion.
Finally, the level of randomness in the network of hormones around GH increases with age. This is common in many other hormonal networks, and is also triggered by fasting in the GH network by lowering IGF-1. This also needs more study.
(((That was a painful paper. I know too little about the subject. The graphs didn't inspire much confidence. Growth hormone isn't that interesting to me. Too many details that I'll forget by next week.)))
Abstract follows:
Interestingness: 2
Paper by JD Veldhuis in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.
(((This issue seems to consist mostly of the papers from the conference on endocrine and molecular interventions in aging reported on in the previous issue. Could get heavy)))
(((First repeat subject: growth hormone. Not one I find particularly interesting)))
Giving growth hormone (GH) to people with GH deficiency helps with many of their problematic psychological symptoms (reduced energy and sense of well-being, social isolation, depressed mood and increased anxiety) and physical symptoms (reduction in lean body mass, bone mineral density, basal metabolic rate, strength, glomerular filtration rate (((kidneys))), increase in body fat and cholesterol). Old people share many of the same problems. Maybe GH would be good for them too. (((The underlying drive in the paper is that increasing growth hormone would be a good thing. Considering the correlation between GH and IGF-1, and it and shortened lifespan, I think the assumption nowadays would be the opposite))). There are some side effects with GH supplementation (fluid retention, myalgia (((muscle pain))), arthralgia (((joint pain))), carpal tunnel syndrome, gynecomastia (((man-boobs))), glucose intolerance) but maybe by triggering it with growth hormone releasing hormone (GHRH) or growth hormone releasing peptides (GHRP) to secrete in its usual pulse-like manner the side-effects can be reduced or eliminated (((as in the previous GH post)))
GH secretion goes down by 50% every seven years in healthy men after hitting 20 years of age (((That's quite a different number from the 14% every decade cited in the previous paper. The graph shown purportedly showing that decline has 21 data points, a line of best fit that looks like it's not going down by half every 7 years after age 35. It also looks like if you were to take the 6 data points of men under 30 out, you'd be left with a horizontal line of best fit))). In pre-menopausal women, the rate of decline is half as fast but it becomes the same as men's after menopause. It is also lower to begin with (((The graph showing young male and female declines of total GH concentration (it integrates concentration over 24 hours) also seems remarkably dodgy for women. Taking out one outlier out of the 32 data points would seem to make it almost flat. Also, these declines are modeled as linear, which doesn't merge with the exponential declines in secretion. I think I'm missing something in the difference between secretion amounts and total concentrations))). The reason for the difference between the sexes is unknown but probably related to estradiol stimulating GH production.
There's also an exponentially declining link between BMI and GH, with a 1.5 kg/m^2 increase leading to a halving of secretion. (((Accompanying dodgy graph, but this one seems reasonable, except for what seems to me to be too little data to be doing exponential regression))) (((Personal hypohypothesis aside: could this be related to why higher BMI doesn't lead to higher mortality even in the presence of the high heart disease risk?))). This interacts with the age link since there's an increase in BMI with age as well. Abdominal fat also dampens the normally strong link between testosterone serum levels and GH secretion, although this dampening isn't as strong in women. The action of testosterone also seems to be by conversion to estradiol.
There are other covariates with age that might influence GH secretion such as fitness, disturbed sleep, different diet, medication, and illness. Little is known about these to be able to differentiate among causes of decline.
I'll skip for a bit to the model of influences presented later since it helps. The model suggested involves a lot of negative feedback loops to stop GH and IGF-1 from being too high. So GH induces IGF-1 which switches GH off. GHRH induces GH secretion, so both GH and IGF-1 turn GHRH off. Somatostatin turns off GH and GHRH secretion so GHRH, GH and IGF-1 all raise somatostatin secretion. Then there are substances that act on GHRH and somatostatin separately. GHRH is raised by GABA-B, galanin, alpha2-adrenergic and the suggested GHRP. Somatostatin is raised by B-2 adrenergic, but lowered by dopamine, serotonin (1-D), L-arginine, muscarinic cholinergic neurotransmission, and the imagined GHRP.
(((The backing of the above confuses me a bit, and is really not very useful, but here it goes))) Pyridostigmine, a cholinergic agonist, given over two days doubles the daily GH secretions by increasing the amount secreted in the pulse, not by increasing rate of pulsing. This link is attenuated with increased body fat. The equivalent of pyridostigmine in sheep stimulates GHRH and triggers a large GH secretions. The paper then suggests that pyridostigmine limits somatostatin, and that this suggests that the reduction in GH with age is due to both an increase in somatostatin and a lack of GHRH.
Alpha-2 adrenergic agonists increase GH in lots of mammals, including the human, partly by increasing GHRH secretion, and possibly by reducing somatostatin. Clonidine, an alpha-2 adrenergic agonist, is a weak GH inducer in humans though. Beta-2 adrenergic agonists lower GH production, and that's believed to be through somatostatin because they lower GH even in the presence of GHRH.
Dopamine is also a GH secretion inducer, but not much is known about how it changes with aging or across sexes. Also, serotoninergic (5-HT) stimulate GH by reducing somatostatin. Galanin also, being more effective in women than in men and the effect decreasing with age. Same with GABA-B, which works better in older women than in men. Corticotropin releasing hormone, leptin and neuropeptide Y are also mentioned as requiring more study (((but I assume they are also inducers of GH secretion)))
(((Back to the main thread))) Most external drivers of higher GH secretion are dampened with age, including GHRH, GHRP, opiates, GABA agonists, fasting, galanin, sleep, exercise,pyridostigmine, L-arginine, clonidine and L-dopa, but some are not, eg insulin-induced hypoglycemia, and combining L-arginine and GHRH or GHRP. This is consistent with somatostatin excess being one of the main culprits in the decline of GH with age since L-arginine hammers somatostatin. But since L-arginine alone doesn't restore the levels of GH fully, too much somatostatin is probably not the only cause, and there is likely a shortfall in GHRH and/or GHRP as well. Combinations of GHRH, synthetic ligands for the GHRP receptor and L-arginine are very effective at raising GH and IGF-1 secretion.
Finally, the level of randomness in the network of hormones around GH increases with age. This is common in many other hormonal networks, and is also triggered by fasting in the GH network by lowering IGF-1. This also needs more study.
(((That was a painful paper. I know too little about the subject. The graphs didn't inspire much confidence. Growth hormone isn't that interesting to me. Too many details that I'll forget by next week.)))
Abstract follows:
A central enigma in neuroendocrine pathophysiology is the virtually uniform, but mechanistically incompletely explicable, attenuation of secretory and trophic activity of the growth hormone (GH)—insulin-like growth factor type I (IGF-I) axis in healthy aging in mammalian species, including the primate and human. Indeed, in humans, the calculated daily GH secretion rate falls approximately 50% every 7 years beginning at age 18 to 21, but this diminution in GH secretion is approximately twofold less rapid in premenopausal women. In contrast, the magnitude of relative GH deficiency appears to be similar in individuals of older (e.g., postmenopausal) age of either gender. Interpreting the mechanisms that underlie such marked attenuation of secretory activity of the GH-IGF-I axis is confounded by endocrinemetabolic covariates that accompany healthy aging, such as an accumulation of (visceral) adiposity, a decline in physical fitness, a reduction in sex steroids, disruption of slow-wave sleep, and concurrent illness and medications. Available clinical investigations point to a partial endogenous GHRH deficiency state, in this so-called somatopause. An important additional age-related fall in brain cholinergic activity (which regulates somatostatin secretion) is likely, thus arguing for combined hypothalamic somatostatin excess and GHRH, GHRP, or both deficiency. This article also evaluates the novel hypothesis that the GH impoverishment of aging is marked by disrupted network function of the GH-IGF-I feedback axis. Given this background, available and new technologies applied in patient-oriented investigations will likely unravel further the presumptively multiple mechanisms that subserve the hyposomatotropism of healthy aging, and begin to address the relative risks and benefits of restoring secretory activity of the aging GH-IGF-I axis.
Tuesday, January 5, 2010
Growth Hormone: A Physiological Fountain of Youth?
Summary: Need more data. Doesn't look encouraging.
Paper by Jason Wolfe in Journal of Anti-Aging Medicine, Volume 1, Number 1, 1998, published by Mary Ann Liebert Inc (it always is, so consider that your final notice)
This is a review paper of the use of growth hormone with respect to preventing/reversing aging. The idea of why it's worth trying is simple: growth hormone (GH) triggers building of protein and growth of tissue in general. It generates muscle, grows your thymus (immune system trainer/storage) and shrinks adipose tissue (fat). Old people become smaller and their tissues shrink. They are also made of fat (40% in over 75s vs 20% in the young and spritely). Their growth hormone levels, coincidentally, drop like a bitch (14% per decade, dunno if that's simple or compound interest).
GH is triggered/upregulated by growth hormone releasing hormone (GHRH). It is also thought to act mostly through the upregulation of IGF-1 (Insulin-like growth factor). (((Since mutations in IGF-1 receptors in mice lead to big life extension effects, and caloric restriction is also probably related to lowering IGF-1 levels, this seems like a big no-no))).
Early smallish experiments injecting GH into over 60 year olds increased muscle mass sometimes, by a little bit, decreased fat content and increased bone density. No cognitive benefits though, and raised blood glucose levels. The effect on muscle mass was also 10 times smaller than doing exercise.
Studies then tried raising GH by going upstream and injecting GHRH (((mainly because it's a simpler/cheaper molecule I think))), but while it triggered GH, they weren't seeing the increases in IGF-1 that they wanted, unless they injected twice a day. Also, IGF-1 trended back to pre-injection levels during the study.
Finally, some small synthetic molecule was found by accident to raise GH levels. It was modified so that it could be sniffed or eaten which is a big benefit over injections. It raises GH, raises IGF-1, doesn't do anything crazy.
(((Conclusion: no obvious data with regards to longevity. The samples were way too small and young to look for mortality differences. All studies here I think were on quite small groups (20 people or less). No obvious benefits with respect to immune system. If it does turn out to be beneficial, the synthetic seems like a nice thing to have. The author is much more upbeat than this though)))
Abstract follows:
Paper by Jason Wolfe in Journal of Anti-Aging Medicine, Volume 1, Number 1, 1998, published by Mary Ann Liebert Inc (it always is, so consider that your final notice)
This is a review paper of the use of growth hormone with respect to preventing/reversing aging. The idea of why it's worth trying is simple: growth hormone (GH) triggers building of protein and growth of tissue in general. It generates muscle, grows your thymus (immune system trainer/storage) and shrinks adipose tissue (fat). Old people become smaller and their tissues shrink. They are also made of fat (40% in over 75s vs 20% in the young and spritely). Their growth hormone levels, coincidentally, drop like a bitch (14% per decade, dunno if that's simple or compound interest).
GH is triggered/upregulated by growth hormone releasing hormone (GHRH). It is also thought to act mostly through the upregulation of IGF-1 (Insulin-like growth factor). (((Since mutations in IGF-1 receptors in mice lead to big life extension effects, and caloric restriction is also probably related to lowering IGF-1 levels, this seems like a big no-no))).
Early smallish experiments injecting GH into over 60 year olds increased muscle mass sometimes, by a little bit, decreased fat content and increased bone density. No cognitive benefits though, and raised blood glucose levels. The effect on muscle mass was also 10 times smaller than doing exercise.
Studies then tried raising GH by going upstream and injecting GHRH (((mainly because it's a simpler/cheaper molecule I think))), but while it triggered GH, they weren't seeing the increases in IGF-1 that they wanted, unless they injected twice a day. Also, IGF-1 trended back to pre-injection levels during the study.
Finally, some small synthetic molecule was found by accident to raise GH levels. It was modified so that it could be sniffed or eaten which is a big benefit over injections. It raises GH, raises IGF-1, doesn't do anything crazy.
(((Conclusion: no obvious data with regards to longevity. The samples were way too small and young to look for mortality differences. All studies here I think were on quite small groups (20 people or less). No obvious benefits with respect to immune system. If it does turn out to be beneficial, the synthetic seems like a nice thing to have. The author is much more upbeat than this though)))
Abstract follows:
During childhood and early adult life, growth hormone (GH), secreted by the anterior pituitary, is involved in the growth of bones and muscles and other organs as well. Aging is characterized by a decrease in muscle mass and bone strength and an increase in adipose, similar to the effects of pathological hyposecretion of GH in the young. Aging is also accompanied by a gradual decrease in the output of GH, like the drying of an internal fountain, until in the eighth decade of life, it is secreted at less than one-fifth of the "youthful" level.
The GH hypothesis of aging posits that with the availability of human recombinant growth hormone and human recombinant insulin-like growth factor-I, which mediates most of the effects of GH, the GH hypothesis has become testable. Initial experiments involving short term administration of GH in a group of elderly men did indeed show modest improvement in lean body mass and adipose tissue. These studies are sometimes—and incorrectly—taken as proof of the correctness of the growth hormone hypothesis of aging. Subsequent year-long studies have shown GH therapy causes significant adverse effects. Other concerns of long-term treatment include possible diabetogenic effects, potential for increased risk of cancer, and high costs (>$10,000/yr). IGF-I, which mediates most of the effects of GH, is also being explored experimentally, but its role as a growth factor raises fears about tumor induction.
Methods being explored to raise GH levels more physiologically include: GHRH, the GH— releasing hormone produced by the hypothalamus; GH-releasing hexapeptides (GHRPs) which stimulate GH secretion via a novel receptor whose normal function is unknown; and orally active aromatic compounds, developed synthetically which mimic the effects of GHRPs. Because of the unknown long-term effects of elevated GH in the elderly, mimetics should be carefully restricted to clinical trials and temporary needs.
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