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Life Extension - Growth Hormone Reverses Aging
Treatment of adults with growth hormone (GH) deficiency with recombinant.

Life Extension magazine republishes abstracts on health and longevity topics in each issue, drawn from research papers originally published in science and medical journals throughout the world.

Bengtsson BA, Eden S; Lonn L; Kvist H; Stokland A; Lindstedt G; Bosaeus I; Tolli J; Sjostrom L; Isaksson OG Department of Medicine, Sahlgrenska Hospital, Medical Faculty, University of Gothenbnrg Sweden. J Clin Endoccrinol Metab (UNITED STATES) Feb. 1993, 76 (2) p309-17. 

In a double blind, cross-over placebo controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body compo-sition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. 

The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered daily at bedtime. One patient was with-drawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bio-electric impedance, and total body potassium combined with total body water assessments.

The Comprehensive Psychological Rating Scale and the Symptom Check List-96 were used to assess any change in psychopathology. After 26 weeks of treatment. adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13% , whereas visceral AT was reduced by 30%. Muscle volume Life Extension 37 JUNE 1997 increased by 2.5 kg (5%; P c 0.05). 

According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bio-electric impedance technique were similar. 

The mean (+/- SD) concentrations of insulin-like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.69 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin. and pro-collagen- III concentrations were signifi-cantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively.

Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 con-centrations had returned to pretreat-ment values. Finally, after 26 weeks of treatment there was a decrease in the Comprehensive Psychological Rating Scale score P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed benefi-cial effects of replacement therapy with GH are of sufficient magnitude to con-sider treatment of GHD adults.

Growth hormone versus placebo treatment for one year in growth hormone deficient adults increase in exercise capacity and normalization of body composition Jorgensen JO; Vahl N; Hansen TB; Thuesen L; Hagen C; Christiansen JS Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, Denmark. Clin Endocrinology (0xf (ENGLAND) Dec. 1996, 45 (6) ~681-8.

OBJECTIVE: Studies with GH substi-tution in GH-deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End-points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m2 per day) versus placebo treatment for 12 months. DESIGN: Twenty-nine patients (mean age 45.5 +/-years) with adult-onset GHD were stud-ied in a double-blind, parallel design.

Measurements of body composition by means of conventional anthropometry bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity and isometric muscle strength were per-formed at baseline and after 12 months treatment. For body composition measurements a control group of 39 healthy, age and sex-matched subjects was included. 

RESULTS Sum of skinfolds (SKF) at 4 sites decreased significantly after GH treatment Total body fat (TBF) as assessed by DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by SKF revealed significantlyhigher levels compared to DEXA and BIA, although all estimates intercorrelated closely. Visceral a nd subcutaneous abdominal fat decreased by 25 and 17%, respectively after GH (P < 0.01) to levels no longer different from the control group. 

CT of the mid thigh revealed a significant reduction in fat tissue and a significant increase in muscle volume after GH treatment, both of which resulted in a normalization of the muscle: fat ratio (%) (placebo: 58:42 baseline) vs. 58:42 (12 months); GH: 66:34 (baseline vs. 72:28 (12 months) (P = 0.002); normal subjects: 67:33 (P < 0.05 when compared to 12 months placebo data)). 

Total body resistance and resistance relative to muscle volume decreased significantly after GH treatment suggesting over-hydration as compared to normal subjects. Exercise capacity (kJ) increased significantly after GH treatment (placebo: 54.7 +/-9.8 (baseline) vs 51.6 +/- 8.2 (12 months); GH: 64.9 +/- 13.3 (baseline) vs 73.5 +/- 13.6 (12 months) (P < 0.05)). 

Isometric quadriceps strength increased after GH but no treatment effect could be detected owing to a small increase in the placebo group. Serum IGF-I levels (microgram/l) were low baseline and increased markedly after GH treatment to a level exceeding that of normal subjects (270 +/- 31 (12 months GH) vs 156 +/- 8 (normal sub-jects (P < 0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The number of adverse effects were higher in the GH group after 3 months, but not after 6 and 12 months.

CONCLUSIONS: (1) The reduction in excess visceral fat during GH substitution is pronounced and sustained: (2) beneficial effects on total body fat, muscle volume and physical fitness can be reproduced during prolonged placebo-controlled conditions: (3) uncontrolled data on muscle strength must be interpreted with caution: (4) a daily GH substitution dose of 2 IU/m2 seems too high in many adult patients. Effects of long-term, low dose growth hormone therapy on immune function and life expectancy of mice.

Khansari DN; Gustad T Department of Veterinary Science/Microbiology, North Dakota State University, Fargo 58105. Mech Ageing Dev. (SWITZERLAND) Jan 1991 ,57 (1) p87-100.

We have studied effects of long-term, low-dose growth hormone therapy on the immune function and life expectan-cy of Balb/c mice. Sixty male Balb/c mice were aged up to the time when they started showing signs of senes-cence and causal death (deaths started
when they became 17 months old). The aged mice were divided into two groupsof 26 mice each. One group received growth hormone (30 micrograms/mouse) subcutaneously twice a week for 13 weeks. 

The control group received an equal volume of saline for the same
period. During this treatment period, 16 control mice died (61%) whereas only 2 of the hormone-treated mice died (7%). Four mice from each group were killed and immunological functions of spleno-cyteswere evaluated. 

Hormone-treated mice had higher stimulation indices for pokeweed mitogen but not for Concanavalin-A. Total IgG production was decreased but IL-l, IL-2 and TNF production was increased. After a lag period of 4 weeks, growth hormone therapy was continued for another 6 weeks. One of the growth hormone treated mice died while the control group no longer existed. Splenocyte functions of the growth hormone treated mice were compared to those of young mice. The results showed no significant difference between cytokine
production (IL-1, IL-2, TNF and IgG) in the young and the hormone treated groups. 

Stimulation induced by con-canavalin- A and pokeweed mitogen
however, was higher in the young group than the old group. The mortality curve obtained suggests that long-term low-dose
growth hormone treatment pro-longs life expectancy. Effects of human hormone in men Rudman D; Feller AG; Nagraj HS;
Gergans GA, Lalitha PY; Goldberg AF; Schlenker RA; Cohn L;
Rudman IW; Mattson DE Department of Medicine, Medical
College of Wisconsin, Milwaukee.

N Engi J Med (UNITED STATES) Jul 5 1990 ,323 (1) p1-6. BACKGROUND. 
The declining activity of the growth hormone-insulin-like growth factor I (IGF-I) axis with advanc-ing
age may contribute to the decrease in lean body mass and the increase in mass of adipose tissue that occur with aging. 

To test this hypothesis, we studied 21 healthy men from 61 to 81 years old who had plasma IGF-I concentrations of less than 350 U per liter during a six-month base-line period and a six-month treatment period that followed During the treatment period. 12 men (group 1) received approximately 0.03 mg of biosynthetic human
growth hormone per kilogram of body weight subcutaneously three times a week, and 9 men (group 2) received no treatment. 

Plasma IGF-I levels were measured monthly. At the end of each
period we measured lean body mass, the mass of adipose tissue, skin thickness (epidermis plus dermis), and bone density at nine skeletal sites. RESULTS. In group 1. the mean plasma IGF-I level
rose into the youthful range of 500 to 1500 U per liter during treatment,  whereas in group 2 it remained below 350 U per liter. 

The administration of human growth hormone for six months in group 1 was accompanied by an 8.8 percent increase in lean body mass, a 14.4 percent decrease in adipose-tissue mass, and a 1.6 percent increase in average lumbar vertebral bone density (P less than 0.05 in each instance). Skin thickness increased 7.1 percent (P = 0.07). 

There was no significant change in the bone density of the radius or proximal femur In group 2 there was no significant change in lean body mass, the

mass of adipose tissue, skin thickness, or bone density during treatment. 

Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occur in old age.

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