Unzipping The Genes Of Aging?

Klotho is an enzyme encoded in humans’ genes—specifically, in the KL gene.

It’s found throughout all living parts of the human body (and can even circulate about in its hormonal form, or come to rest in its membranaceous form), and its subgroups are especially found:

• α-klotho: in the brain
• β-klotho: in the liver
• γ-klotho: in the kidneys

Great! Why do we care?

Klotho, its varieties and variants, its presence or absence, are very important in aging.

Almost every biological manifestation of aging in humans has some klotho-related indicator; usually the decrease or mutation of some kind of klotho.

Which way around the cause and effect go has been the subject of much debate and research: do we get old because we don’t have enough klotho, or do we make less klotho because we’re getting old?

Of course, everything has to be tested per variant and per system, so that can take a while (punctuated by research scientists begging for more grants to do the next one). Given that it’s about aging, testing in humans would take an incredibly long while, so most studies so far have been rodent studies.

The general gist of the results of rodent studies is “reduced klotho hastens aging; increased klotho slows it”.

(this can be known by artificially increasing or decreasing the level of klotho expression, again something easier in mice as it is harder to arrange transgenic humans for the studies)

Here’s one example of many, of that vast set of rodent studies:

Suppression of Aging in Mice by the Hormone Klotho

Relevance for Alzheimer’s, and a science-based advice

A few years ago (2020), an Alzheimer’s study was undertaken; they noted that the famous apolipoprotein E4 (apoE4) allele is the strongest genetic risk factor for Alzheimer’s, and that klotho may be another. FGF21 (secreted by the liver, mostly during fasting) binds to its own receptor (FGFR1) and its co-receptor β-klotho. Since this is a known neuroprotective factor, they wondered whether klotho itself may interact with β-amyloid (Aβ), and found:

❝Aβ can enhance the ability of klotho to draw FGF21 to regions of incipient neurodegeneration in AD❞

~ Dr. Lehrer & Dr. Rheinstein

In other words: β-amyloid, the substance whose accumulation is associated with neurodegeneration in Alzheimer’s disease, is a mediator in klotho bringing a known neuroprotective factor, FGF21, to the areas of neurodegeneration

In fewer words: klotho calls the firefighters to the scene of the fire

Read more: Alignment of Alzheimer’s disease amyloid β-peptide and klotho

The advice based on this? Consider practicing intermittent fasting, if that is viable for you, as it will give your liver more FGF21-secreting time, and the more FGF21, the more firefighters arrive when klotho sounds the alarm.

See also: Intermittent Fasting: What’s the truth?

…and while you’re at it:

Does intermittent fasting have benefits for our brain?

A more recent (2023) study with a slightly different (but connected) purpose, found results consistent with this:

Longevity factor klotho enhances cognition in aged nonhuman primates

…and, for that matter this (2023) study that found:

Associations between klotho and telomere biology in high stress caregivers

…which looks promising, but we’d like to see it repeated with a sounder method (they sorted caregiving into “high-stress” and “low-stress” depending on whether a child was diagnosed with ASD or not, which is by no means a reliable way of sorting this). They did ask for reported subjective stress levels, but to be more objective, we’d like to see clinical markers of stress (e.g. cortisol levels, blood pressure, heart rate changes, etc).

A very recent (April 2024) study found that it has implications for more aspects of aging—and this time, in humans (but using a population-based cohort study, rather than lab conditions):

The prognostic value of serum α-klotho in age-related diseases among the US population: A prospective population-based cohort study

Can I get it as a supplement?

Not with today’s technology and today’s paucity of clinical trials, you can’t. Maybe in the future!

However… The presence of senescent (old, badly copied, stumbling and staggering onwards when they should have been killed and eaten and recycled already) cells actively reduces klotho levels, which means that taking supplements that are senolytic (i.e., that kill those senescent cells) can increase serum klotho levels:

Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans

Ok, what can I take for that?

We wrote about a senolytic supplement that you might enjoy, recently:

Fisetin: The Anti-Aging Assassin

Want to know more?

If you have the time, Dr. Peter Attia interviews Dr. Dena Dubal (researcher in several of the above studies) here:

Click Here If The Embedded Video Doesn’t Load Automatically

Enjoy!

Move Over, Leaky Gut. Now It’s A Leaky Brain.

…which is not a headline that promises good news, and indeed, the only good news about this currently is “now we know another thing that’s happening, and thus can work towards a treatment for it”.

Back in February (most popular media outlets did not rush to publish this, as it rather goes against the narrative of “remember when COVID was a thing?” as though the numbers haven’t risen since the state of emergency was declared over), a team of Irish researchers made a discovery:

❝For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system may be the key drivers of brain fog associated with long covid❞

~ Dr. Matthew Campbell (one of the researchers)

Let’s break that down a little, borrowing some context from the paper itself:

• the leaky blood vessels are breaching the blood-brain-barrier
  • that’s a big deal, because that barrier is our only filter between our brain and Things That Definitely Should Not Go In The Brain™
• a hyperactive immune system can also be described as chronic inflammation
  • in this case, that includes chronic neuroinflammation which, yes, is also a major driver of dementia

You may be wondering what COVID has to do with this, and well:

• these blood-brain-barrier breaches were very significantly associated (in lay terms: correlated, but correlated is only really used as an absolute in write-ups) with either acute COVID infection, or Long Covid.
• checking this in vitro, exposure of brain endothelial cells to serum from patients with Long Covid induced the same expression of inflammatory markers.

How important is this?

As another researcher (not to mention: professor of neurology and head of the school of medicine at Trinity) put it:

❝The findings will now likely change the landscape of how we understand and treat post-viral neurological conditions.

It also confirms that the neurological symptoms of long covid are measurable with real and demonstrable metabolic and vascular changes in the brain.❞

~ Dr. Colin Doherty (see mini-bio above)

You can read a pop-science article about this here:

Irish researchers discover underlying cause of “brain fog” linked with long covid

…and you can read the paper in full here:

Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment

Want to stay safe?

Beyond the obvious “get protected when offered boosters/updates” (see also: The Truth About Vaccines), other good practices include the same things most people were doing when the pandemic was big news, especially avoiding enclosed densely-populated places, washing hands frequently, and looking after your immune system. For that latter, see also:

Beyond Supplements: The Real Immune-Boosters!

Take care!