Gero 310 F'08 endocrine 2

Gero 310 F'08 endocrine 2 - Age changes in the endocrine...

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Unformatted text preview: Age changes in the endocrine system normal aging is characterized by robust deficits in many aspects of endocrine function why/how is endocrine function impaired in normal aging?- several factors involved: 1. Reduction in levels of hormone being secreted- multiple causes: alterations in detection and or secretion mechanisms, atrophy of gland- common age-related endocrine impairment 3. Fewer hormone receptors on target tissues 2. Altered responsiveness (e.g., cell signaling) to hormones age-related changes in hormone levels reduced levels of:- GH & IGF-1- melatonin- thymosin- estrogen- testosterone- DHEA- calcitonin hormones act on all tissues in the body hormones have numerous vital, beneficial effects decreased levels with age in several key hormones suggests a potential contributory role in the aging process idea: replace depleted hormones halt aging & restore youth hormone replacement therapies Are hormones reasonable therapeutic targets? 1. Reduction in levels of hormone being secreted: testosterone- aka androgen deficiency in aging males ( ADAM)- colloquially: andropause Baker et al., (1976) Clin. Endocrinol. Baker et al., (1976) Clin. Endocrinol.- decrease in bioavailable testosterone of ~ 50% from 20 y through 80 y - bioavailable T below normal limit: * 7% of 40-60 y * 20% of 60-80 y * 35% of 80+ y - increase in sex hormone binding globulin (SHBG) which binds T- reduces amount of free T and bioavailable T (loosely bound to albumin)- also, compensatory increase in luteinizing hormone (LH)- a variety of behavioral and cognitive effects related to ADAM: - impairments in mood- poorer memory skills (esp. spatial skills)- sense of well-being- fatigue- increased risk of Alzheimers disease- reduction in muscle strength, body composition- reduction in muscle mass - reduced libido and sexual function- men >35 yrs have reduced fertility potential- increased risk of coronary artery disease - increased risk of osteoporosis- reduced bone mass Androgen actions: sites affected by treatment Androgens are endogenous regulators of neuron viability hippocampal neurons show more cell loss with toxic insult after depletion of androgens by gonadectomy (GDX) androgen treatment largely blocks GDX effect-how vulnerable you are Ramsden et al (2003) Neuroscience Androgens have beneficial effects in brain Pike (2001) Brain Res. Androgens are endogenous regulators of neuron viability testosterone protects neurons from cell death caused by - amyloid (implicated in AD)-red are dead; green is alive cells Androgens have beneficial effects in brain Moffatt & Resnick (2007) Neurobiol. Aging testosterone increases brain activity men with higher T levels showed higher levels of rCBF in hippocampus and other brain regions indicates higher T is associated with higher brain activation implicates T in cognition Androgens have beneficial effects in brain Androgens have beneficial effects in brain Leranth et al. (2004) Leranth et al....
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This note was uploaded on 01/16/2011 for the course GERO 310 taught by Professor Davies during the Fall '09 term at USC.

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Gero 310 F'08 endocrine 2 - Age changes in the endocrine...

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