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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 Alzheimer’s 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 ß- 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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Gero 310 F'08 endocrine 2 - Age changes in the endocrine...

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