Effects of aging on serum ionized and cytosolic free calcium: relation to hypertension and diabetes.

Elevated cytosolic free calcium (Ca(i)) and reciprocally reduced, extracellular ionized calcium (Ca-ion) levels are observed in both hypertension and non-insulin-dependent diabetes mellitus (NIDDM). Because the changes of vascular function and insulin sensitivity in these conditions resemble the changes associated with "normal" aging, we wondered to what extent similar alterations in calcium metabolism occur with aging per se in the absence of overt hypertension or diabetes. We therefore measured platelet Ca(i) levels by spectrofluorometry and serum Ca-ion levels in normotensive, nondiabetic, healthy, normal, elderly (>65 years old) subjects, mean age +/-SEM, 72.2+/-1.5 years old (n=11); in healthy, normal, young (<65 years old) adults, 46.1+/-2.3 years old (n=12); in 10 young adult hypertensives, 48.6+/-1.9 years old; and in 10 normotensive NIDDM subjects, 49.2+/-1.6 years old. Platelet Ca(i) levels were higher (104.5+/-4.9 versus 80.2+/-1.8 nmol/L, P<0.01) and Ca-ion levels lower (1.212+/-0.010 versus 1.236+/-0.011 mmol/L, P<0.05) in normal elderly compared with young control subjects, but normal elderly Ca(i) and Ca-ion levels were indistinguishable from those in hypertensive (Ca(i) 107.5+/-3.6 nmol/L, Ca-ion 1.210+/-0.009 mmol/L) and NIDDM (Ca(i) 110.7+/-4.7 nmol/L, Ca-ion 1.204+/-0.014 mmol/L) subjects. In normal subjects, significant correlations were found between platelet Ca(i) levels and age (r=0.655, P<0.01) and between Ca(i) levels and systolic blood pressure (r=0.733, P<0.001). We conclude that aging is associated with alterations of Ca(i) and Ca-ion levels resembling those changes present at any age in hypertension and type 2 diabetes. We hypothesize that these alterations of calcium metabolism underlie the predisposition to the alterations of blood pressure and insulin sensitivity characteristic of "normal" aging. The data also suggest that studies of the aging process should be limited to subjects with normal blood pressure and glucose tolerance.