The Klotho gene is gaining increasing attention for its anti-aging properties. The latest installment of this series explores the potential cognitive benefits of administering her Klotho to both mice and monkeys, and the results may translate to humans. But the benefits of this circulating hormone extend beyond the brain.
Klotho was first discovered as an anti-aging gene in 1997, and researchers found that increasing its expression could extend the lifespan of mice by more than 30%. Various genetic and environmental factors can affect lifespan, but studies have shown that Klotho-deficient mice not only live shorter lives, but also experience more age-related complications. Premature aging in these mice was often accompanied by loss of muscle and adipose tissue, thinning skin, reduced fertility, cardiovascular complications, movement abnormalities and bone disease. Since klotho is produced primarily in the kidneys, it is not surprising that many of these age-related complications result from kidney dysfunction.
Kidneys produce two types of Klotho. They are (1) transmembrane proteins that insert into cell membranes and mediate renal function, and (2) secretory hormones that are released into the bloodstream. People with naturally higher levels of hormones in their blood appear to live longer, be more resistant to age-related complications, and have better learning and memory abilities. In fact, animal studies have shown that even relatively small doses of Klotho can produce significant changes in the brain, allowing more connections in the brain’s learning and memory center, the hippocampus.
However, hormones as large as Klotho cannot cross the blood-brain barrier. Instead, it relies on intercellular signaling.a University of California team San Francisco found that Klotho promotes glutamate signaling in the NMDA learning pathway. In the presence of glutamate, NMDA proteins are activated to promote synaptic plasticity, a process essential for learning and memory. Klotho circulating in the blood is thought to cross the blood-brain barrier and cause the release of glutamate, an effect that continues to provide long-lasting effects once the hormone is removed. This not only prevents cognitive decline, but may also reverse cognitive decline.
Beyond learning and memory, the mechanisms by which Klotho can resist other age-related changes have been largely unknown until now. In a recent study they published, Chinese researcher Introducing Klotho into the bloodstream was found to reduce inflammation and oxidative stress in both the kidney and brain. Given that inflammation is one of the major contributors to age-related complications, their findings make the Klotho gene a promising therapeutic target for treating chronic inflammation, not to mention helping individuals live longer. suggests that it may be
The study recruited a cohort of 8-month-old mice, which corresponds to approximately 40 years in humans. Compared to saline-injected control mice, the Klotho-enhanced group had significantly lower levels of kidney inflammation and oxidative damage. Although hormone injections did not directly increase the amount of Klotho in the brain, these mice also developed resistance to age-related neuroinflammation and improved performance in a battery of water maze tasks that measure learning and memory.
To understand Klotho’s effects at the cellular level, the researchers also obtained RAW264.7 tissue samples known to express a specific type of inflammatory cell called macrophages. Macrophages are a type of white blood cell recruited to fight infections. These cells can take two forms of her. M1 macrophages release proinflammatory factors to kill foreign pathogens, but these toxins can also damage healthy cells. Once the pathogen is cleared, signaling alterations trigger conversion of M1 macrophages to her M2 subtype. M2 macrophages are responsible for repairing and regenerating damaged tissues. The researchers speculate that in chronic inflammatory conditions, the effects of M1 macrophages are prolonged and their conversion to the M2 subtype is prevented.
Surprisingly, Wang et al. found that exposure to Klotho significantly reduced the number of pro-inflammatory M1 macrophages and enhanced the activity of anti-inflammatory M2 macrophages. These findings were reflected in both the brain and kidney of Klotho-enhanced mice. The researchers concluded that Klotho hormone stimulates a signaling pathway that drives this conversion, but the exact mechanism remains unclear.
Although Klotho’s role in mediating inflammation remains an active area of research, its potential for therapeutic efficacy is promising. Understanding the role of this protein may reveal the secret to preventing aging. The future where Klotho hormones can be packaged and sold as a supplement may be closer than we think.
