HEALTH NEWS

Study Title:

Junk Food, Phosphate, and Aging

Study Abstract

Identifying factors that accelerate the aging process can provide important therapeutic targets for slowing down this process. Misregulation of phosphate homeostasis has been noted in various skeletal, cardiac, and renal diseases, but the exact role of phosphate toxicity in mammalian aging is not clearly defined. Phosphate is widely distributed in the body and is involved in cell signaling, energy metabolism, nucleic acid synthesis, and the maintenance of acid-base balance by urinary buffering. In this study, we used an in vivo genetic approach to determine the role of phosphate toxicity in mammalian aging. Klotho-knockout mice (klotho-/-) have a short life span and show numerous physical, biochemical, and morphological features consistent with premature aging, including kyphosis, uncoordinated movement, hypogonadism, infertility, severe skeletal muscle wasting, emphysema, and osteopenia, as well as generalized atrophy of the skin, intestine, thymus, and spleen. Molecular and biochemical analyses suggest that increased renal activity of sodium-phosphate cotransporters (NaPi2a) leads to severe hyperphosphatemia in klotho-/- mice. Genetically reducing serum phosphate levels in klotho-/- mice by generating a NaPi2a and klotho double-knockout (NaPi2a-/-/klotho-/-) strain resulted in amelioration of premature aging-like features. The NaPi2a-/-/klotho-/- double-knockout mice regained reproductive ability, recovered their body weight, reduced their organ atrophy, and suppressed ectopic calcifications, with the resulting effect being prolonged survival. More important, when hyperphosphatemia was induced in NaPi2a-/-/klotho-/- mice by feeding with a high-phosphate diet, premature aging-like features reappeared, clearly suggesting that phosphate toxicity is the main cause of premature aging in klotho-/- mice. The results of our dietary and genetic manipulation studies provide in vivo evidence for phosphate toxicity accelerating the aging process and suggest a novel role for phosphate in mammalian aging.

From press release:

Here's another reason to kick the soda habit. New research published online in the FASEB Journal shows that high levels of phosphates may add more "pop" to sodas and processed foods than once thought. That's because researchers have found that the high levels of phosphates accelerate signs of aging. High phosphate levels may also increase the prevalence and severity of age-related complications, such as chronic kidney disease and cardiovascular calcification, and can also induce severe muscle and skin atrophy.

"Humans need a healthy diet and keeping the balance of phosphate in the diet may be important for a healthy life and longevity," said M. Shawkat Razzaque, M.D., Ph.D., from the Department of Medicine, Infection and Immunity at the Harvard School of Dental Medicine. "Avoid phosphate toxicity and enjoy a healthy life."

To make this discovery, Razzaque and colleague examined the effects of high phosphate levels in three groups of mice. The first group of mice was missing a gene (klotho), which when absent, causes mice to have toxic levels of phosphate in their bodies. These mice lived 8 to 15 weeks. The second group of mice was missing the klotho gene and a second gene (NaPi2a), which when absent at the same time, substantially lowered the amount of phosphate in their bodies. These mice lived to 20 weeks. The third group of mice was like the second group (missing both the klotho and NaPi2a genes), except they were fed a high-phosphate diet. All of these mice died by 15 weeks, like those in the first group. This suggests that phosphate has toxic effects in mice, and may have a similar effect in other mammals, including humans.

"Soda is the caffeine delivery vehicle of choice for millions of people worldwide, but comes with phosphorous as a passenger" said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "This research suggests that our phosphorous balance influences the aging process, so don't tip it."

Study Information

1.M. Ohnishi, M. S. Razzaque.
Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging.
The FASEB Journal,
2010 April
Department of Medicine, Infection and Immunity at the Harvard School of Dental Medicine