Is NaHCO 3 an antiaging elixir ?

EVOLVING EVIDENCE supports that deviation from normal toward the acid spectrum of the acid-base balance is associated with premature death compared with patients with a normal acidbase status. Patients with nondialysis-dependent chronic kidney disease (CKD) and metabolic acidosis have increased mortality compared with CKD patients without metabolic acidosis (5, 9). Furthermore, the risk for mortality and adverse cardiovascular outcomes increases in CKD patients as plasma total CO2 decreases due to metabolic acidosis, and this increased risk extends into the normal range for plasma total CO2 (9). Diets in developed societies are largely acid producing due to comparatively higher intake of acid-producing animalsourced protein compared with base-producing plant-sourced protein, the latter including fruits and vegetables (10). Consequently, individuals in developed societies are typically subjected to a constant dietary acid challenge with potential pathological consequences that might be ameliorated by a dietary acid reduction. Human aging involves a complex set of pathophysiological processes that often lead to cardiovascular disease, the leading cause of premature death in developed societies (3). Cardiovascular disease is mediated predominantly by arteriosclerosis, which involves medial calcification due to altered osteogenesis, including altered mineral, mostly calcium and phosphate, metabolism (2, 4). Consequently, there is much interest in elucidating mechanism(s) for these processes, particularly vascular calcification. CKD is a human model of accelerated aging given the shorter lifespans of CKD patients (11), mediated in large part by higher rates of cardiovascular disease (11), which includes vascular injury with calcification (4). The k1/k1 mouse, with deficient expression of the klotho gene, is an animal model of accelerated aging (6). Kidneys are the main source of klotho (1, 4), klotho expression is considerably reduced in CKD patients with a reduced glomerular filtration rate (GFR) (1), and klotho deficiency is associated with vascular osteoinduction, which is well described in CKD (4). Accompanying their dramatic reduction in lifespan, klotho-deficient animals have marked arteriosclerosis with extensive medial calcification, tissue calcification, and increased plasma levels of aldosterone (5, 6). Consequently, klotho deficiency might mediate premature death in CKD, possibly through accelerated arteriosclerosis with medial calcification. In addition, klotho deficiency appears to be a laboratory model in which to test interventions purported to reduce aspects of aging, particularly vascular calcification, in an effort to ameliorate the progression of these processes in conditions like CKD, which is associated with premature death. Recently, Leibrock and colleagues (7) examined the effects of HCO3 supplementation as 150 mM NaHCO3 drinking solution in klotho hypomorphic (kl/kl) mice on growth, lifespan, various aspects of pathology, and serum levels of selected hormones, including aldosterone. A previous study (8) from their laboratory showed that dietary NaCl or treatment with the mineralcorticoid receptor antagonist spironolactone increased the lifespan of these animals. The latter data suggest that volume depletion (previously shown to be a feature of this model) and/or aldosterone (previously shown to be increased in this model) contributed to its shorter lifespan. The effect of spironolactone was also associated with decreased vascular calcification. Interestingly, Leibrock and colleagues (8) showed that NH4Cl, which added metabolic acidosis to underlying respiratory acidosis due to the emphysema that characterizes the k1/k1 model, abrogates tissue calcification and increases the lifespan of these animals. The investigators attributed this beneficial effect to alkalinization of acidic intracellular compartments, supported by higher plasma NH3 associated with NH4Cl intake, of kl/kl mice rather than to extracellular acidemia because plasma pH was unchanged by NH4Cl in kl/kl animals. Because kl/kl mice had respiratory acidosis with acidemia, they subsequently examined the effect of NaHCO3, which might alkalinize both extracellular and intracellular compartments. The authors reported that NaHCO3 increased lifespan, reduced vascular calcification as well as reduced calcification in the trachea, lung, and intestine, reduced plasma levels of aldosterone and antidiuretic hormone, increased plasma pH through increasing plasma HCO3 concentration but not changing PO2, increased phosphaturia, and decreased plasma PO4 3