Unlocking Klotho: A Gateway to Healthy Aging and Cognition
Written on
Chapter 1: The Journey of Aging
Aging is a multifaceted process characterized by numerous changes. From the swift growth of infancy to the transformations during puberty, these shifts continue throughout life. Adulthood, in particular, does not mark the end of change; rather, it leads us through the distinct phases of middle and old age, each with its own biological challenges.
Regrettably, the changes that accompany aging are often less than favorable for many. Our immune defenses weaken, the likelihood of cancer increases, muscles deteriorate, joints become rigid, and memory may falter. Additionally, alterations occur in our microbiome, skin, and body composition. At the molecular level, even our DNA starts to exhibit signs of decline.
Despite the ongoing mystery surrounding the biology of aging, researchers are gradually uncovering markers that can provide insight into how our bodies cope with the relentless passage of time. Although epigenetic clocks are gaining popularity, monitoring specific protein levels can also offer valuable warnings about potential health issues.
One such protein is klotho.
Klotho was identified in 1997 and derives its name from the Greek goddess of fate, who spins the thread of life. This transmembrane protein is embedded within cell membranes, particularly in the brain, liver, and kidneys. Interestingly, klotho can detach from these membranes, circulating freely and influencing a variety of signaling pathways, including those related to calcium balance, insulin regulation, and neural plasticity.
Klotho and Aging
Research indicates that levels of circulating klotho decline as humans age. Conversely, individuals possessing a particular gene variant that boosts klotho production appear to have a reduced risk of developing dementia and Alzheimer’s disease, even if they carry the genetic predisposition associated with APEO4. Furthermore, studies show that administering additional klotho to mice—either through gene modification or injections—can mitigate many age-related issues and extend their lifespan by approximately 15-20%.
Klotho in Rhesus Macaques
A recent study further supports the potential of klotho in promoting cognitive resilience and health in older age. This research bridges the gap between experiments conducted on mice and observational studies in humans, recognizing that while mice provide useful insights, they are not a perfect model for human aging.
In this study, researchers assessed the effects of low-dose subcutaneous klotho injections in rhesus macaques, which age similarly to humans, experiencing cognitive decline and structural brain changes, particularly in regions such as the hippocampus and prefrontal cortex. Initial tests showed that injecting the rhesus version of klotho protein into mice yielded beneficial outcomes, enhancing synaptic plasticity and improving working memory within just four hours. This suggests that klotho may be evolutionarily conserved among mammals, indicating its importance from an evolutionary standpoint.
In the study involving macaques, which were approximately 22 years old—comparable to a human aged 65—the researchers observed a significant increase in klotho levels following a 10 µg/kg dosage. Comparing the results from those receiving klotho versus a placebo, they noted:
- Enhanced cognitive performance in aged rhesus macaques during both normal and high memory load tasks.
This improvement persisted for at least two weeks and was consistent across both genders. Notably, higher doses of klotho did not yield greater benefits, suggesting there is an optimal range for its effectiveness.
Cautions and Considerations
While these findings are promising, it’s important to note that the study focused on only one cognitive aspect, and the long-term effects of klotho on lifespan remain unknown. Nevertheless, the potential for sustaining cognitive function in later years is encouraging.
Boosting Klotho Levels
How can we enhance our klotho levels? Currently, there are no known medical treatments for klotho injections available to the public. However, traditional methods such as exercise and a healthy diet can be beneficial. A comprehensive analysis found that:
- Engaging in exercise training increases soluble klotho levels, regardless of an individual's health status or the specific exercise regimen used.
Although the studies employed various protocols, the optimal "klotho-boosting" exercise routine is still unclear. Both resistance and aerobic training generally appeared effective.
Diet, naturally, remains a topic of debate. Recent cross-sectional studies suggest that higher klotho levels correlate with increased intake of carbohydrates, sugars, dietary fibers, vitamin D, folates, and copper.
This correlation does not advocate for excessive sugar consumption; rather, it highlights the importance of balanced nutrition. For instance, fruits are rich in fiber and sugars, while vegetables provide essential nutrients like folate. The link between insulin—often seen as a negative factor—and klotho is intriguing, as insulin may facilitate the conversion of the membrane-bound form of klotho into its circulating form, which is associated with cognitive benefits.
It’s important to recognize that these findings are correlational, so causation cannot be definitively established. There may be overlap between individuals who exercise and those who consume more fruits and vegetables.
Interestingly, the nutritional associations with klotho levels appear to vary by gender. Women's klotho levels showed a stronger connection to higher carbohydrate and sugar intake alongside lower alcohol consumption, while men benefited more from increased dietary fibers, phosphorus, and potassium.
Conclusion: Keep Klotho Levels High
The research surrounding klotho and its potential for enhancing healthy aging continues to evolve. Keeping klotho levels elevated may be beneficial for cognitive health in older age.
In this video, Dr. Carmela Abraham discusses the role of klotho in longevity and its implications for healthy aging.
Dena Dubal elaborates on the connection between klotho, cognition, brain aging, and Alzheimer’s disease, shedding light on this promising area of research.