Glucagon-Like Peptide 1 (GLP-1) in Diabetes and Aging

By David D'Alessio in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, 2000.

Interestingness: 2

I'd never heard of GLP-1, but it seems to accentuate the glucose-lowering effect of insulin, by including but maybe not limiting to, increasing insulin secretion. Maybe also acts as a satiety marker. GLP-1 is synthesised in the intestines. Glucose eaten has much higher effect on increasing insulin than glucose injected.  Lots of problems in studies caused by mixing detection of active and inactive form of the peptide.

Giving up and Adrenal Andropause and Aging

Writing even the half-arsed summaries takes too long, so I'm giving up on those.  From now on, it will be most likely down to an interestingness score, tags and a one line summary, mainly for me to keep track of them.  Also, no more abstract cut-n-pasting, since it probably is not as legit as I thought it was before.


So, Adrenal Andropause and Aging, by Samuel SC Yen,  in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, 2000.

Interestingness: 2

Nice review on cortisol changes with aging and DHEA/DHEA-S changes with aging, and how they diverge, cortisol going up and DHEA-S going down, post adrenopause (30s), even though they are both produced by the adrenal glands. Mentions possible link to immune system (DHEA-S inversely correlated to IL-6)

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.


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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.

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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.

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.


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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.

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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.

About-Daily (Circadian) and About-Weekly (Circaseptan) Patterns of Human Salivary Melatonin

Summary: Chronobiology weekly.

Interestingness: 1

Paper by Manfred Herold, Germaine Cornélissen, Mary Jo Rawson, George S. Katinas, Cheryl Alinder, Chris Bratteli, Denis Gubin, Franz Halberg in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.


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They analysed the melatonin and cortisol content of the saliva of five people 29-73 years of age for a week. They think there's a weekly cycle in melatonin, peaking on Tuesday. I'm close-minded.
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Abstract follows:

Circadian rhythms in circulating, urinary, salivary, pineal, pituitary and hypothalamic melatonin have been mapped. About weekly (circaseptan) rhythms, mapped previously in several other species, are demonstrated herein for human saliva, in individuals of widely differing ages. Whether or not the now demonstrated decrease with age in the circadian amplitude of human adults is accompanied by an increase in the circaseptan amplitude, as it is the case for blood pressure, remains to be determined.

Serum Schiff Bases Are Elevated in Patients with Dementia

Summary: Schiff bases are more prevalent in demented people's blood, whatever that means. Lipid peroxide levels are lower, whatever that means as well.

Interestingness: 2

Paper by Aleksandra Musial, Tadeusz Pietras And Dariusz Nowak in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.


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Straight forwards report of testing of four oxidation markers in the blood of 30 old people with clear dementia compared against 18 old people without clear dementia. Conjugated dienes (CnH(2n-2) for values of n, wikipedia tells me) were at about the same concentration in both groups; TBARS (ThioBarbituric Acid Reactive Substances, formed by lipid peroxidation, again, thanks wikipedia) were about 20% higher in demented, but not significant to the 0.05 standard; lipid peroxides were three and a half times higher in the non-demented, and Schiff bases were about 80% higher in the demented.

They are obviously trying to claim higher oxidation levels in the demented. Schiff bases fits their model (I didn't look into how they form). The lower lipid peroxides doesn't, so they come up with reasons. They also find lower lipid peroxides with age in the non-demented group. One possible excuse: lower amounts of poly-unsaturated fatty acids in the brains of older people, supposedly found by someone else.

Anyway, not very interesting, but bonus points for the cool abstract.
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Abstract follows:

Hypothesis

Increased oxidative stress may accompany diseases of the central nervous system either as a perpetrator or merely as the result of tissue damage in the course of neurodegeneration. The brain is especially susceptible to damage mediated by reactive oxygen species because it has a high rate of oxygen consumption and contains large amounts of readily oxidizable substrates, such as polyunsaturated fatty acids. Indices of systemic oxidative stress, including serum lipid-peroxidation products, may be greater in dementia than in normal aging.


Methods

Study groups consisted of 30 patients with dementia and 18 healthy age-matched controls. All patients underwent neuropsychological testing and qualified for the study on the basis of history, physical examination, complementary laboratory tests, and brain computed tomography scan. Serum levels were assessed for the following lipid-peroxidation products: conjugated dienes, lipid peroxides, thiobarbituric acid reactive substances, and Schiff bases.


Results

There were two statistically significant differences in serum levels of lipid-peroxidation products between the study groups. Lipid peroxides were significantly lower (0.34 Å 0.09 U532/mL versus 1.12 Å 0.96 U532/mL, p = 0.000055), while Schiff bases were statistically higher (589.4 Å 267.3 AU/mL versus 329.0 Å 107.5 AU/mL, p = 0.000282) in the subjects with dementia. There were statistically significant correlations between all measured products of lipid peroxidation in the controls and between all products of lipid peroxidation except for Schiff bases in the subjects with dementia. Cognitive impairment did not correlate with levels of lipid-peroxidation products. Age correlated negatively with Mini-Mental State Examination score and lipid peroxides in healthy controls.


Conclusion

More final fluorescent products of lipid peroxidation (Schiff bases) were found in subjects with dementia than in healthy controls, implying that oxidative stress is increased in dementia. Our data suggests a decrease in lipid peroxides during normal aging.

Serum Thiols as a Surrogate Estimate of DNA Repair Correlates to Mammalian Life Span

Summary: Mammalian species with higher thiol fractions in their protein live longer

Interestingness: 2

Paper by Ronald W Pero, Catharina Hoppe and Yezhou Sheng in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.


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These people grabbed blood samples from mostly one or two specimens of 17 different mammalian species (mouse, rat, wolf, dog, goat, sheep, rabbit, bear, cat, lynx, musk ox, fallow deer, cow, gorilla, chimpanzee, horse and human) and precipitated the proteins in those samples. They found a correlation (r=0.819) between the proportion of thiol in the precipitate and the lifespan of the species (not the specimen, they didn't measure how long the actual specimen they took blood from lived), and a stronger correlation (r=0.841) between the proportion of thiols in the thiol-rich fraction of the proteins and the lifespan of the species.

The plots don't look as good as the r-numbers would indicate because they are heavily influenced by the human specimens since they were many more of them (25 vs 1 or 2 of each of the others), and they are out there way on the right in the lifespan axis (they were assigned a lifespan of 95 years). The graphs don't look horrible either.

Their theoretical explanation confuses me. They are saying that this shows that creatures with higher lifespan have lower oxidation levels. I don't know if they are saying that this is being shown directly, that is oxidation would get rid of the thiol (this assumes that their measuring of the thiols wouldn't count oxidised thiols in them), or that this is being shown indirectly, that is if high lifespan animals didn't have lower oxidisation levels their higher thiol-fractioned proteins would be more affected by oxidation, their enzymes would not work, and so these animals wouldn't have high lifespans. I think they mean the second explanation, but I'm not sure. Backing this second interpretation, is them pointing at the unoxidised thiol-dependence of poly adenosine diphosphate-ribose polymerase (PARP), a DNA-repair enzyme, and from there making other claims about the link between mutation, DNA repair and oxidative stress.
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Abstract follows:

Biologically occurring thiols are a sensitive estimate of the reduction/oxidation balance of cells, being easily and reversibly converted from sulfhydryl to disulfide structures in proteins and amino acids. Thiols are also known to regulate DNA repair, especially via the influence on poly (adenosine diphosphate-ribose) polymerase activity. Here the thiol content of saturated ammonium sulphate-precipitated proteins from sera was correlated to a mammalian life span of 17 species. A close correlation was established between the thiol-rich proteins and the life span of the mammals (r = 0.841, p < 0.001). These data provide a strong scientific connection between mechanisms of DNA repair and oxidative stress leading to DNA damage accumulation and mutation, which may be important to the aging process.