Hormones and the Hormones and the Effects on Anti-agingEffects on Anti-aging

By: Michelle Klewer and By: Michelle Klewer and Elizabeth McGhee Elizabeth McGhee

IntroductionIntroduction

Multiple hormones decrease with Multiple hormones decrease with increasing age.increasing age.

It is hypothesized that hormone It is hypothesized that hormone replacement therapy will reverse replacement therapy will reverse or prevent effects of aging.or prevent effects of aging.

Common hormones studied:Common hormones studied:– Dehydroepiandrosterone (DHEA)Dehydroepiandrosterone (DHEA)– TestosteroneTestosterone– Human growth hormone (HGH)Human growth hormone (HGH)– MelatoninMelatonin

Dehydroepiandrosterone Dehydroepiandrosterone (DHEA)(DHEA)

DHEA is a precursor for DHEA is a precursor for androstenedione which then androstenedione which then converts to testosterone, converts to testosterone, dihydrotestosterone and estradiol. dihydrotestosterone and estradiol.

The adrenal gland, gonads, The adrenal gland, gonads, adipose tissue and brain produces adipose tissue and brain produces DHEA from pregnenolone. DHEA DHEA from pregnenolone. DHEA has a sulfate-bound form (DHEAS) has a sulfate-bound form (DHEAS)

In 70-80 year olds’, DHEA is only In 70-80 year olds’, DHEA is only 10-15% of the concentrations in 10-15% of the concentrations in younger individualsyounger individuals

Low levels has been hypothesized Low levels has been hypothesized to be linked to diabetes, to be linked to diabetes, osteoporosis, weight gain, heart osteoporosis, weight gain, heart failure, and cognitive deficits failure, and cognitive deficits (Celec & Starka, 2002). (Celec & Starka, 2002).

Uses Uses

Has been used to treat:Has been used to treat:– lupus erythematosuslupus erythematosus– rheumatoid arthritis rheumatoid arthritis

Evidence of anti-agingEvidence of anti-aging

Increases in bone mineral density Increases in bone mineral density and decreases in bone resorptionand decreases in bone resorption

Body compositionBody composition– Decreases in body massDecreases in body mass– Increases in fat-free massIncreases in fat-free mass

Decreases in oxidative stress Decreases in oxidative stress

Bone mineral Density Bone mineral Density (BMD)(BMD) 50 mg daily oral dose of DHEA to 55 50 mg daily oral dose of DHEA to 55

men and 57 women between the ages of men and 57 women between the ages of 55-85 years 55-85 years

They found that the after 1 year women They found that the after 1 year women who received the daily dose compared who received the daily dose compared to a placebo group had an increase in to a placebo group had an increase in bone mineral density in the lumbar bone mineral density in the lumbar spine and a slight decrease in bone spine and a slight decrease in bone resorption (von Mresorption (von Mühühlen et al, 2008). len et al, 2008).

BMD cont.BMD cont.

DHEA oral dose of 75mg and DHEA oral dose of 75mg and 50mg for men and women for 2 50mg for men and women for 2 years.years.

Women had an increase in bone Women had an increase in bone mineral density of the distal mineral density of the distal radius and men had an increase radius and men had an increase in the femoral neck (Nair et in the femoral neck (Nair et al.,2006).al.,2006).

Body Composition Body Composition

In the study by von MIn the study by von Mühühlen et al, body len et al, body compositon was measured before and compositon was measured before and after administration of DHEA and there after administration of DHEA and there were no significant changes.were no significant changes.

Another study conducted on different Another study conducted on different aged rats found a decrease in body aged rats found a decrease in body weight for the oldest rats that received weight for the oldest rats that received DHEA for 1 month (Kumar et al, 2008). DHEA for 1 month (Kumar et al, 2008).

Nair et al. also looked at the Nair et al. also looked at the effects of DHEA on body effects of DHEA on body composition.composition.

They did not measure a They did not measure a significant change in weight but significant change in weight but there was an increase in fat-free there was an increase in fat-free mass for both elderly men and mass for both elderly men and women women

Oxidative StressOxidative Stress

DHEA for 1 month on different DHEA for 1 month on different aged rats resulted in decreases of aged rats resulted in decreases of MAO activity and lipofuscin MAO activity and lipofuscin (Kumar et al, 2008). (Kumar et al, 2008).

Other EffectsOther Effects

Physical performance Physical performance Aerobic capacityAerobic capacity Quality of lifeQuality of life Insulin sensitivityInsulin sensitivity All had no significant changes All had no significant changes

after DHEA for 2 years in elderly after DHEA for 2 years in elderly (Nair et al., 2006). (Nair et al., 2006).

Testosterone Testosterone

Testosterone is a sex hormone Testosterone is a sex hormone that regulates male sex that regulates male sex characteristics and sex drive characteristics and sex drive (Goodman, Fuller, Boissonnault, (Goodman, Fuller, Boissonnault, 2003). 2003).

Harman et al. 2001 showed that Harman et al. 2001 showed that levels of testosterone decreased levels of testosterone decreased with increased age in males with increased age in males

Testosterone Testosterone continued…continued… Ferrando et al., 2002, twelve Ferrando et al., 2002, twelve

healthy elderly males either healthy elderly males either received testosterone enanthate received testosterone enanthate or a placebo for 6 months or a placebo for 6 months

subjects received injections once subjects received injections once a week and then for the a week and then for the remainder of the study they remainder of the study they received injections twice a week received injections twice a week

Testosterone Testosterone continued…continued… At the end of 6 months the elderly At the end of 6 months the elderly

males who received testosterone males who received testosterone had an overall increase in lean had an overall increase in lean body mass and a decrease in total body mass and a decrease in total body fat percentage body fat percentage

the treatment group had the treatment group had increased strength scores based increased strength scores based on 1RM (Ferrando et al., 2002) on 1RM (Ferrando et al., 2002)

Testosterone Testosterone continued…continued… Giannoulis et al., 2008 investigated the Giannoulis et al., 2008 investigated the

effects of testosterone on body effects of testosterone on body composition, skeletal muscle gene composition, skeletal muscle gene expression aerobic capacity using expression aerobic capacity using transdermal patches of testosterone for 6 transdermal patches of testosterone for 6 months. months.

After 6 months there were no significant After 6 months there were no significant changes in body composition, CSA of the changes in body composition, CSA of the middle thigh, VO2 max, muscle strength middle thigh, VO2 max, muscle strength and muscle gen transcript levels and muscle gen transcript levels

Growth HormoneGrowth Hormone

Growth hormone is produced by Growth hormone is produced by the anterior pituitary gland and is the anterior pituitary gland and is known for its actions in inducing known for its actions in inducing skeletal growth and visceral skeletal growth and visceral growth by regulating metabolism growth by regulating metabolism of proteins, carbohydrates and of proteins, carbohydrates and lipids. lipids.

GH continued…GH continued…

In one study conducted, subjects were given In one study conducted, subjects were given 0.003 mg/kg/day injections of GH for the first 0.003 mg/kg/day injections of GH for the first 8 weeks of the study and then from 8 to 48 8 weeks of the study and then from 8 to 48 weeks were given levels to keep their insulin-weeks were given levels to keep their insulin-like growth factor I (IGF-I) within a reference like growth factor I (IGF-I) within a reference range adjusted for age and sex. range adjusted for age and sex.

The GH administration was found to increase The GH administration was found to increase lean body mass (LBM), decrease in body fat lean body mass (LBM), decrease in body fat mass, in LDL-cholesterol and total cholesterol mass, in LDL-cholesterol and total cholesterol and improvements in quality of life within 48 and improvements in quality of life within 48 weeks of GH treatment (Chihara et al., 2008). weeks of GH treatment (Chihara et al., 2008).

A trend of increases in LBM as a result of GH is A trend of increases in LBM as a result of GH is confirmed in a study by Giannoulis et al., confirmed in a study by Giannoulis et al., 2008. 2008.

MelatoninMelatonin

Melatonin is a hormone produced Melatonin is a hormone produced in the pineal gland. in the pineal gland.

It’s main function is to regulate It’s main function is to regulate circadian rhythms such as the circadian rhythms such as the sleep-wake cycle. sleep-wake cycle.

Melatonin levels decrease as age Melatonin levels decrease as age increases thus effecting natural increases thus effecting natural circadian rhythms. circadian rhythms.

Oxidative stressOxidative stress

Has been hypothesized to decrease Has been hypothesized to decrease oxidative stressoxidative stress

Daily doses of melatonin was Daily doses of melatonin was administered to mice for 3 months. administered to mice for 3 months.

Lipid peroxidation was measured in the Lipid peroxidation was measured in the brain, liver, spleen and kidneys and the brain, liver, spleen and kidneys and the experimental group of mice who had experimental group of mice who had the melatonin dose had values of that the melatonin dose had values of that of young mice (Manda & Bhatia, 2003). of young mice (Manda & Bhatia, 2003).

Adverse Effects of Adverse Effects of Hormone TherapyHormone Therapy DHEADHEA

– chest pain, hot flashes, and palpitations chest pain, hot flashes, and palpitations (Celec & Starka, 2003; von M(Celec & Starka, 2003; von Müühlen et hlen et al.,2008).al.,2008).

TestosteroneTestosterone– skin irritation and nipple tenderness skin irritation and nipple tenderness

(Giannoulis et al., 2008). (Giannoulis et al., 2008). Growth HormoneGrowth Hormone

– pain, joint stiffness (Giannoulis et al., pain, joint stiffness (Giannoulis et al., 2008), upper respiratory infection, 2008), upper respiratory infection, emotional liability, abnormal thinking and emotional liability, abnormal thinking and psychotic depression (Chihara et al., 2007). psychotic depression (Chihara et al., 2007).

So…Do they work?So…Do they work?

The studies have some trends The studies have some trends towards increases in BMD and towards increases in BMD and increases in lean body mass but increases in lean body mass but more studies need to be performed.more studies need to be performed.

The majority of oxidative stress The majority of oxidative stress studies have been performed on studies have been performed on animals, therefore more human trials animals, therefore more human trials are necessary to conclude any are necessary to conclude any effects.effects.

REFERENCESREFERENCES Baydas, G., Yasar, A., and Tuzcu, M. Comparison of the impact of melatonin on chronic ethanol-Baydas, G., Yasar, A., and Tuzcu, M. Comparison of the impact of melatonin on chronic ethanol-

induced learning and memory impairment between young and aged rats. induced learning and memory impairment between young and aged rats. J. Pineal ResearchJ. Pineal Research 2005; 39:346-352.2005; 39:346-352.

Celec, P., Stárka, L. Dehydroepiandrosterone- is the fountain of youth drying out? Celec, P., Stárka, L. Dehydroepiandrosterone- is the fountain of youth drying out? Physiol. ResPhysiol. Res. . 2003; 52: 397-407. 2003; 52: 397-407.

Chihara, K., Kato, Y., Kohno, H., Takano, K., Tanaka, T., Teramoto, A., Shimatsu, A. Safety and Chihara, K., Kato, Y., Kohno, H., Takano, K., Tanaka, T., Teramoto, A., Shimatsu, A. Safety and efficacy of growth hormone (GH) during extended treatment of adult Japanese patients with GH efficacy of growth hormone (GH) during extended treatment of adult Japanese patients with GH deficiency (GHD). deficiency (GHD). Growth Hormone and IGF ResearchGrowth Hormone and IGF Research 2008; 18: 307-317. 2008; 18: 307-317.

Ferrando, A., Sheffield-Moore, M., Yeckel, C., Gilkison, C., Jiang, J., Achacosa, A., Lieberman, S., Ferrando, A., Sheffield-Moore, M., Yeckel, C., Gilkison, C., Jiang, J., Achacosa, A., Lieberman, S., Tipton, K., Wolfe, R., Urban, R. Testosterone administration to older men improves muscle Tipton, K., Wolfe, R., Urban, R. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. function: molecular and physiological mechanisms. Am J Physiol Endocrinal MetabAm J Physiol Endocrinal Metab 2002; 282: 2002; 282: E601-E607.E601-E607.

Giannoulis, M., Jakcson, N., Shojaee-Moradie, F., Nair, K., Sonksen, P., Martin, F., Umpleby, A. Giannoulis, M., Jakcson, N., Shojaee-Moradie, F., Nair, K., Sonksen, P., Martin, F., Umpleby, A. The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal muscle gene expression in healthy elderly men: a randomized controlled trial. muscle gene expression in healthy elderly men: a randomized controlled trial. J Clin Endocrinol J Clin Endocrinol MetabMetab 2008; 93(8): 3066-3074. 2008; 93(8): 3066-3074.

Goodman, C., Fuller, K., Boissonnault, W. (2003). Goodman, C., Fuller, K., Boissonnault, W. (2003). Pathology: implications for the physical Pathology: implications for the physical therapisttherapist. Pennsylvania: Elsevier.. Pennsylvania: Elsevier.

Harman, S., Metter, E., Tobin, J., Pearson, J., Blackman, M. Longitudinal Effects of aging on Harman, S., Metter, E., Tobin, J., Pearson, J., Blackman, M. Longitudinal Effects of aging on serum total and free testosterone levels in healthy. serum total and free testosterone levels in healthy. J of Endocrinol and MetabJ of Endocrinol and Metab 2001; 86: 724- 2001; 86: 724-731.731.

Horowitz, S. Human growth hormone and antiaging medicine. Horowitz, S. Human growth hormone and antiaging medicine. Alternative and complementary Alternative and complementary therapiestherapies 2003: 163-169. 2003: 163-169.

Kumar, P., Taha, A., Sharma, D., Kale, R., Banquer, N. Effect of dehydroepiandrosterone (DHEA) Kumar, P., Taha, A., Sharma, D., Kale, R., Banquer, N. Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions. regions. BiogerontologyBiogerontology 2008; 9:235-246. 2008; 9:235-246.

Manda, K., Bhatia, A. Melatonin-induced reduction in age related accumulation of oxidative Manda, K., Bhatia, A. Melatonin-induced reduction in age related accumulation of oxidative damage in mice. damage in mice. BiogerontologyBiogerontology 2003; 4:133-139. 2003; 4:133-139.

Nair, K., Rizza, R., O’Brian, P., Dhatariya, K., Short, K., Nehra, A., Rittone, J., Klee, G., Basu, A., Nair, K., Rizza, R., O’Brian, P., Dhatariya, K., Short, K., Nehra, A., Rittone, J., Klee, G., Basu, A., Cobelli, C., Toffolo, G., Man, C., Tindall, D., Melton, L., Smith, G., Khosla, S., Jensen, M. DHEA in Cobelli, C., Toffolo, G., Man, C., Tindall, D., Melton, L., Smith, G., Khosla, S., Jensen, M. DHEA in elderly women and DHEA or testosterone in elderly men. elderly women and DHEA or testosterone in elderly men. New England J of MedNew England J of Med 2006; 2006; 355(16):1647-1659.355(16):1647-1659.

Poeggeler, B. Melatonin, aging, and age-related disease. Poeggeler, B. Melatonin, aging, and age-related disease. EndocrineEndocrine 2005; 27(2):201-212. 2005; 27(2):201-212. von Mühlen, D., Laughlin, G., Kritz-Silverstein, D., Bergstrom, J., Bettencourt, R. Effect of von Mühlen, D., Laughlin, G., Kritz-Silverstein, D., Bergstrom, J., Bettencourt, R. Effect of

dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. composition in older adults: the DAWN trial. Osteoporosis Int Osteoporosis Int 2008; 19:699-707.2008; 19:699-707.