Archive for the ‘IGF / IGFBP’ Category

Insulin Levels and Life Span Studies

Tuesday, December 14th, 2010

Sci. Aging Knowl. Environ., 4 August 2004
Vol. 2004, Issue 31, p. re5
[DOI: 10.1126/sageke.2004.31.re5]

REVIEWS

Murine Models of Life Span Extension

Jason K. Quarrie, and Karl T. Riabowol

The authors are in the Department of Biochemistry and Molecular Biology at the University of Calgary, Calgary, Alberta, Canada, T2N 4N1. E-mail: karl@ucalgary.ca (K.T.R.)

http://sageke.sciencemag.org/cgi/content/full/2004/31/re5

Key Words: life span extension • mouse models • growth hormone • insulin-like growth factor • oxidative damage • caloric restriction

Abstract: Mice are excellent experimental models for genetic research and are being used to investigate the genetic component of organismal aging. Several mutant mice are known to possess defects in the growth hormone/insulin-like growth factor 1 (GH/IGF-1) neurohormonal pathway and exhibit dwarfism together with extended life span. Their phenotypes resemble those of mice subjected to caloric restriction. Targeted mutations that affect components of this pathway, including the GH receptor, p66Shc, and the IGF-1 receptor (IGF-1R), also extend life span; mutations that affect IGF-1R or downstream components of the pathway decouple longevity effects from dwarfism. These effects on life span may result from an increased capacity to resist oxidative damage.

Citation: J. K. Quarrie, K. T. Riabowol, Murine Models of Life Span Extension. Sci. Aging Knowl. Environ. 2004 (31), re5 (2004)

source: http://sageke.sciencemag.org/cgi/content/abstract/2004/31/re5

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Calorie-restriction, Protein-restriction and free-IGF-1 / SHBG

Monday, November 22nd, 2010

Studies pertaining to Calorie-restriction (CR), Protein-restriction (PR) and free-IGF-1 and SHBG.

1)

Br J Cancer. 2000 Jul;83(1):95-7.
Hormones and diet: low insulin-like growth factor-I but normal bioavailable androgens in vegan men.

Allen NE, Appleby PN, Davey GK, Key TJ.
Cancer Epidemiology Unit, Imperial Cancer Research Fund, Radcliffe Infirmary, Oxford, UK.

Abstract

Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002).

Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone.

PMID: 10883675 [PubMed - indexed for MEDLINE]PMCID: PMC2374537

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http://www.ncbi.nlm.nih.gov/pubmed/10883675

Full text PDF: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374537/pdf/83-6691152a.pdf
PDF file: Hormones and diet-83-6691152a.pdf

2)

Aging Cell. 2008 Oct;7(5):681-7.
Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans.

Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO.

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Free-IGF-1 lowers SHBG | Acne, Polycystic Ovarian Syndrome, Hyperinsulinemia and Diet

Sunday, November 21st, 2010

1)

Arch Dermatol. 2002 Dec;138(12):1584-90.
Acne vulgaris: a disease of Western civilization.

Cordain L, Lindeberg S, Hurtado M, Hill K, Eaton SB, Brand-Miller J.
Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80523, USA. cordain@cahs.colostate.edu
Comment in:
* Arch Dermatol. 2002 Dec;138(12):1591-2.
* Arch Dermatol. 2003 Jul;139(7):941; author reply 942-3.
* Arch Dermatol. 2003 Jul;139(7):941-2; author reply 942-3.

Abstract

BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne.

OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed.

CONCLUSIONS: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.

PMID: 12472346 [PubMed - indexed for MEDLINE]

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Men with vertex balding have lower circulating levels of IGFBP-3 and higher levels of IGF-1

Sunday, November 21st, 2010

J Am Acad Dermatol. 2000 Jun;42(6):1003-7.
Vertex balding, plasma insulin-like growth factor 1, and insulin-like growth factor binding protein 3.

Platz EA, Pollak MN, Willett WC, Giovannucci E.

Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
Abstract

BACKGROUND: A recent report suggested that men with vertex balding have higher levels of plasma insulin-like growth factor 1 (IGF-1). The association of its major carrier protein, insulin-like growth factor binding protein 3 (IGFBP-3), with male pattern hair loss has not been examined.

OBJECTIVE: We evaluated the relations of plasma concentrations of IGF-1 and IGFBP-3 with vertex balding in middle-aged and elderly men.

METHODS: Participants were 431 male members of the Health Professionals Follow-up Study who responded to a question in 1992 on their hair pattern at 45 years of age and who were 47 to 81 years old when they provided a blood specimen in 1993-1994. Odds ratios (ORs) of vertex balding associated with IGF-1 and IGFBP-3 were estimated from logistic regression models mutually adjusting for each other and controlling for age at blood draw.

RESULTS: Of the 431 men, 128 had vertex balding at age 45. Compared with men who were not balding, for a 1 standard deviation increase in plasma IGF-1 level (72.4 ng/mL), the OR for vertex balding was 1. 31 (95% CI, 0.95-1.81). For a 1 standard deviation increase in plasma IGFBP-3 (957 ng/mL), the OR for vertex balding was 0.62 (95% CI, 0.44-0.88).

CONCLUSION: Older men with vertex balding have lower circulating levels of IGFBP-3 and higher levels of IGF-1 when controlling for IGFBP-3 level.

PMID: 10827403 [PubMed - indexed for MEDLINE]

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Is IGF-1 Linked to Diseases?

Sunday, November 21st, 2010

You will find many studies linking an increase in IGF-I concentrations with the risk of prostate, bladder, colorectal, and breast cancers.. Thus, one would expect to aim at lowering IGF-1.

I asked myself if IGF-1 was a causing agent of cancer or if it was simply a symptom of something else (another causing factor) that causes cancer (and hair loss) … A legit question, don’t you think? I am all for solving the problem at the root, dealing with the real issue not trying to lower “numbers” .. we need to know exactly what the numbers mean.

In the case of IGF-1 it seems, we need it in our system, too little causes dysfunction, too much causes dysfunction.

I was not the only one to question if IGF-1 was a reliable predictor of cancers or hair loss:

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IGF-1 and Prostate Cancer: An Insubstantial Link

A study headed by June Chan at Harvard University links the growth protein insulin-like growth factor type-1 (IGF-1) with prostate cancer, but many health professionals caution against drawing quick conclusions. Methods used by Chan to assess this risk, including adjustment for other prostate cancer risk factors like smoking and the cancer-protective protein IGFBP-3, lead to questions regarding the accuracy of the conclusions drawn from this study. According to growth hormone clinical researcher Dr. L.E. Dorman, “In my experience, PSA [a widely accepted marker for prostate cancer] levels consistently drop 50% over a period of a month or two of growth hormone secretagogue therapy.” Growth hormone–popularized for its anti-aging effects–works by stimulating IGF-1 production.

Dorman, the co-author of Growth Hormone: Reversing Human Aging Naturally, also points out that IGF-1 is produced by cells of the immune system, which may be stimulated in the presence of cancer. “To conclude that IGF-1 stimulates the initiation of prostate cancer goes against everything that we know about its positive effects on the immune system, which protects against cancer. To make any substantial conclusions about the effects of these hormones on prostate cancer, a study should include the use of growth hormone therapy with prostate cancer patients.

Dr. L. Cass Terry, a long-time researcher of growth hormone notes the complete lack of cancer incidence in any of his growth hormone treated patients, “With 800 people over the age of about 40, you would think that given the normal incidence rate of cancer, some of these people would get cancer. It could be that there is some sort of protective effect from growth hormone replacement”. Terry and his associate Dr. Edmund Chein report the results of growth hormone treatment on a man who came to them with prostate cancer, indicating that without any usual forms of treatment like surgery, the patients’ levels dropped from the 50 to 60 range down to 5 to 7 (men with prostate cancer usually show levels of PSA in the 10 to 20 range). It has been hypothesized that these effects come from stimulatory effects on the immune system that result from growth hormone therapy.

Pharmacologist James Jamieson, who headed the development of a growth hormone secretagogue, notes the importance of using growth hormone therapy in a way that keeps IGF-1 within a healthy range. “When stimulated to release growth hormone, the body has mechanisms that typically keep IGF-1 within a normal range.”

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IGF-1 is Linked to Cancers, Heart Disease, Type 2 Diabetes and Osteoporosis

Friday, November 19th, 2010

Insulin-like growth hormone (IGF-1) is believed to be linked to Cancers, Heart Disease, Type 2 Diabetes and Osteoporosis. It could be used to predict the risk of these disease. OR does it?

The link does exist:

decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents.

Source: Aging Cell. 2008 Oct;7(5):681-7. – Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans.

Plasma levels of insulin-like growth factor I (IGF-I) have been associated with risk of several cancers.

Source: Cancer Epidemiol Biomarkers Prev. 2002 Sep;11(9):852-61 – Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations.

Variation in the circulating concentrations of the insulin-like growth factor (IGF) system has been implicated in the etiology of chronic diseases including cancer (prostate, breast, colon, and lung), heart disease, type 2 diabetes, and osteoporosis

..

The results of this study lend additional support to the hypothesis that circulating IGF-I concentrations increase the risk of prostate, bladder, colorectal, and breast cancer

Source: Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):739-46. Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women. (more…)

Protein is a Stimulator of Free IGF-1

Friday, November 19th, 2010

It seems that protein (in meat or dairy) is a stimulator of free-IGF-1

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Aging Cell. 2008 Oct;7(5):681-7.
Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans.

Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO.

Division of Geriatrics & Nutritional Sciences, Washington University School of Medicine, St Louis, MO 63110, USA. lfontana@dom.wustl.edu

Abstract

Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown.

Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg(-1) of body weight per day to 0.95 g kg(-1) of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL(-1) to 152 ng mL(-1).

These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.

Source: http://www.ncbi.nlm.nih.gov/pubmed/18843793
Full: http://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2008.00417.x/full

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