August 24, 2007

Aging: Gender Bias, Hormones and Biomarkers

Women, on the whole, live longer than men. But, in them, declining estrogen levels usher menopause. With menopause, the chances of osteoporosis (bone demineralization leading to fractures and bone pain) and cardiovascular diseases (like heart attack and arterial diseases: estrogen elevates HDL levels, the good cholesterol; and reduces LDL levels, the bad cholesterol) increase drastically. This can be alleviated by exogenous administration of estrogen, in the form of skin patch, for example. But the concomitant risks of cancer should be borne in mind. Fertility comes to an end with menopause. This actually is a blessing in disguise, since reduced fertility would reduce maternal mortality (an aged mother is more likely to suffer complications of childbirth) and would curtail the risks of fetal malformations (which rises with both maternal and paternal age).

Glucocorticoids, such as cortisol, are hormones released in response to stress, such as physical and mental stress, have been implicated in aging. Their level rises in blood with aging, and this is due to the faulty sensing mechanism in a brain area called hippocampus. Hippocampus senses glucocorticoid levels and calculates the amount of this steroid to be secreted, by negative feedback, in much the same way the 'gain' if an 'electronic amplifier' is regulated by negative feedback. Rising glucocorticoid levels with age damages this feedback control mechanism, with consequent production of still more glucocorticoids and this vicious cycle repeats. This is 'glucocorticoid cascade hypothesis' theory of aging. Catecholamines, such as adrenaline (epinephrine), nor-adrenaline (norepinephrine) are stress hormones and they raise the heart rate and overall metabolism. They initiate the 'fight and flight' response and raise the blood glucose level. They too, seem to play a role in aging.

Growth hormone (somatotropin/GH) administration restores muscle mass and vigor, and so does hormones such as DHEA, testosterone (in males); but hormone supplementations have their own risks. You might ask, how do we know that we are aging? Is there any biochemical or radiological test to quantify it? The answer is no, presently, but a few 'indices' like cross-linking of collagen, insulin resistance, free testosterone (male), DHEAS (dehydro epi androsterone-sulfate), fibrinogen level, body mass index or BMI (female), handgrip strength, graying of hair and a few others have been proposed.
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