Klotho, The Genetic Spinner of Aging Destiny
Indeed, we are all destined to age, but some age better than others. Some age faster and some slower. A gene called Klotho appears to be the cause. Klotho seems a rather strange name for a gene, but it comes from the name of one of the triad of Greek Goddesses known as the Fates, those independent controllers of destiny, to whom even the gods must submit. The genetic Klotho was accidentally discovered as the missing gene that caused premature aging in a group of transgenic mutated laboratory mice. Many studies implicated of the lack of Klotho in disease processes, including kidney disease. Newer studies have shown the protective qualities the presence of Klotho provides on reducing oxidative stress, improving blood pressure and preserving the retina in the eye. Klotho can slow aging and prevent loss of mental abilities. Now the newest study shows additional Klotho promotes neuroprotection in the brain.
A team of researchers for Boston University has recently published their study findings in the Journal of Biological Chemistry showing the neuroprotective effect of Klotho against Alzheimer’s disease. They grew nerve cells in petri dishes in the laboratory. Klotho was added to some of the dishes. When amyloid, like that which is found to accumulate in the neurons of Alzheimer’s disease, was added to all the dishes, the ones with the added Klotho showed a much higher survival rate of nerve cells than the untreated dishes. Carmela Abraham, Ph.D.is the principal investigator of this study and a professor of biochemistry and pharmacology at Boston University Medical Center. She says “We now have evidence that if more Klotho is present in the brain, it will protect the neurons from the oxidative stress induced by amyloid and glutamate. Finding a neuroprotective agent that will protect nerve cells from amyloid that accumulates as a function of age in the brain is novel and of major importance.”
However, it is not possible to introduce Klotho directly as a pill or an injection as it is a large molecule that cannot cross the blood-brain barrier. A compound of smaller molecules that can cross the blood-brain barrier and increase the levels of Klotho in the brain is presently under development. Dr. Abraham believes that “increasing Klotho levels with such compounds would improve the outcome for Alzheimer’s patients, and if started early enough would prevent further deterioration. This potential treatment has implications for other neurodegenerative disease such as PARKINSON’S, Huntington’s, ALS and brain trauma, as well.”
E. Zeldich, C.-D. Chen, T. A. Colvin, E. A. Bove-Fenderson, J. Liang, T. B. Tucker Zhou, D. A. Harris, C. R. Abraham. The Neuroprotective Effect of Klotho is Mediated via Regulation of Members of the Redox System. Journal of Biological Chemistry, 2014; DOI: 10.1074/jbc.M114.567321
Review by Marcia McCall