Hey guys! Lance here. And this video will be the second one that I’ve done on longevity news.
In trying to keep up with the latest news,
I’ve pulled together some short stories that I think might be of interest to you guys.
So stay tuned.
I want to start out by saying that this last weekend was RAADFest,
and the video that I post next Tuesday will be about RAADFest and the things that I learned at RAADFest.
But this video is about the news.
So, here’s the stories that we’ll be covering in today’s video.
The first is about the supplement AKG and it’s recent addition to the list of anti-aging supplements.
The next is about the impact of resistance training on older individuals who are trying to build new muscle,
and ways to improve that effect.
Third is about a study that shows that genomic instability has more of an impact on aging
than researchers previously thought.
And finally, a look at some studies that examine the effect of genetics on longevity.
This first story is about some fairly recents studies involving AKG, or alpha-ketoglutarate.
AKG has been a popular sports supplement, and it’s often used in the world of bodybuilding.
Now it's getting some interest in the field of longevity and aging research, due to its central role in metabolism.
AKG was discovered in 1937 by Hans Adolph Krebs and William Arthur Johnson at the University of Sheffield.
AKG was part of the discovery and identification of the citric acid cycle, commonly known as the Krebs cycle.
The Krebs cycle is a series of chemical reactions that are used to generate energy, in the form of ATP, in the mitochondria.
AKG is a naturally occurring “endogenous intermediary metabolite”, which means that our bodies can create it.
The supplement industry manufactures a form of synthetic AKG,
but manufactured molecules of AKG are chemically identical to the natural ones.
So, what does AKG do?
AKG is a molecule that's critical because it regulates the overall speed of the Krebs cycle.
It's also involved in a number of cellular and metabolic pathways.
It's an energy donor and a cellular signaling molecule involved in intracellular communication.
It's also a nitrogen scavenger and can prevent nitrogen overload and the buildup of excess ammonia.
It regulates some of the processes involved in DNA methylation, and as such,
it plays an important role in gene regulation and expression.
It plays a role as a precursor in amino acid production and is a key source of glutamate and glutamine,
which stimulates protein synthesis and inhibits protein degradation in the muscles.
There is a lot of evidence that AKG can influence aging, and this is backed up by a number of studies.
One was a 2014 study which showed AKG can extend the lifespan of an adult round worm called C. elegans by roughly 50%,
by inhibiting ATP synthase and the target of rapamycin.
Another study that came out on September 1st of this year,
demonstrated that AKG supplementation improved both the lifespan and the health span of middle-aged mice.
In the C elegans study, it was found that AKG not only increased lifespans but also delayed certain age-related phenotypes.
It did this to a couple of pathways, and one of them was the inhibition of ATP synthase,
which is an enzyme that is essential to the production of ATP.
By inhibiting ATP synthase, mitochondrial production of ATP is slowed down,
and this partial suppression of ATP production is responsible for increased life spans in C. elegans.
The key appears to be reducing mitochondrial function just enough without going so far as to be detrimental.
Inhibition of the mTOR pathway has been shown to slow down the aging process in multiple species.
AKG doesn't interact directly with mTOR, but it does influence it through the inhibition of ATP synthase.
AKG depends at least partially on AMPK and FOXO proteins.
When the AMP to ATP ratio is too high, AMPK is activated, and this inhibits the mTOR pathway,
allowing the cell to adjust its metabolism and balance its energy reserves effectively.
FOXO regulates the impact of insulin and growth factors
and its activation can also suppress mTOR signaling.
Autophagy, which can be activated by both fasting and inhibition of mTOR,
is also significantly increased by AKG supplementation.
In the more recent mouse study,
the researchers administered a calcium salt of AKG to mice that were 18 months old,
which is the equivalent of human middle-age.
They continued to dose these mice throughout the rest of their lives.
Now, the gains in lifespan were relatively modest,
with a 10% gain for female mice and 5% gain for male mice.
Since it’s possible to significantly extend the life spans of mice using other methods,
this was not a particularly impressive result.
What was more impressive was the effects of AKG on the health span of the mice.
As the mice proceeded into old age, the untreated mice became much more frail, much more quickly.
The treated mice became frail much more slowly, and ultimately became much less frail than the untreated mice,
right up until the end of their lives, which were delayed slightly by the AKG.
While frailty is usually a pretty good indictor of mortality in untreated mice,
it was much less effective at predicting mortality in the treated mice.
The graying and loss of hair, which is one of the primary indicators of aging in humans,
was also noticeably improved in the treated mice.
AKG supplementation may also boost respiration and reduce chronic inflammation.
Metabolism and aging are known to be tightly connected,
and while AKG supplementation has been shown to be of limited utility in boosting longevity,
every little bit helps… Right?
But what really important here is the extension of the health span… right up to when they died.
Since AKG is already sold as a pretty inexpensive supplement,
it seems like it might be a worthwhile addition to our toolbox to fight aging.
Next we’re going to take a look at a study that examines the impact of resistance training on muscle mass in older individuals.
Loss of muscle mass and strength is a particular problem as we get older.
This phenomenon has been called sarcopenia, and it results in the loss of mobility and independence.
Exercise, particularly resistance training,
has been shown to be beneficial in counteracting the age-associated loss of muscle mass and function.
But the growth of new muscle tissue in response to resistance training is attenuated in older individuals…
the result of the same processes that lead to sarcopenia.
After reading the paper,
a guy that a lot of you might be familiar with, who uses the handle “Reason”,
reviewed the study on his website, “Fight aging".
He noted that the use of senolytic therapies to destroy harmful, inflammatory senescent cells
was one of a few technologies that might address the situation…
and that the use of senolytics was not addressed in the study.
Instead, this study seemed to focus on well-established ways of altering the metabolism of muscle tissue
to optimize the anabolic response of skeletal muscles to resistance training in the elderly.
And it did this primarily through the use of supplemental therapies
that have the potential to combine with resistance training to increase muscle mass.
Things like physical nutrition, creatine, anti-inflammatory drugs, testosterone,
and growth hormone.
And it seemed to conclude that combining supplemental therapies with resistance training
only had modest results at best in growing new muscle.
So, it appears that more research is required in this field.
Next, a study published in the July issue of the journal “Cell”,
provides a new perspective on the links between aging, age related diseases,
and genomic instability… one of the primary hallmarks of aging.
This study examines the differences in mutations between somatic cells and germ cells.
So, germ cells are cells found in the sexual organs that produce sperm and eggs;
somatic cells are all the cells in the body, except for the germ cells.
Mutations in germ cells are one of the driving forces behind evolution.
Organisms with harmful mutations tend to die off,
while organisms with beneficial mutations, pass those mutations on to future generations.
This results in the diversity of life we experience on the planet today.
But mutations also occur within the somatic cells, and these are the mutations that this study examines.
These mutations to the somatic cells cause damage to the DNA
and this damage is known as genomic instability.
It is one of the primary hallmarks of aging, and it has a negative impact on several downstream hallmarks.
In this study, the researchers call the differences between cells somatic mosaicism.
These types of mutations are apparently more common in somatic cells than in germ cells,
because germ cells have defenses against mutation that somatic cells do not.
So, when mutations happen inside somatic cells,
some of them can favor mutated cells over ordinary cells.
For example, when skin cells get exposed to UV radiation and mutate,
these mutated cells can outcompete the ordinary cells.
While not yet cancerous, these mutated cells are more prone to cancer than normal cells.
These types of mutations also appear to happen in lung cells, leading to COPD in smokers,
and in blood and arterial cells, leading to atherosclerosis.
The researchers in this study point out that a relationship exists
between heritable genetic diseases and aging,
because some of these diseases require both inherited DNA
and somatic mutations in order to occur.
It's possible that these genetic mutations can cause cells to lose the ability to properly process proteins
or to remove them when they are to diseased.
It’s also possible that these mutated cells could lead to proteostasic diseases such as Alzheimer’s.
Since genomic instability is one of the most difficult hallmarks to cure,
a direct link between genomic instability and age-related diseases isn't good
because there's not much that can be done about it… yet.
On the other hand,
finding out that aging is driven more by genomic instability than most researchers previously thought,
could possibly lead to new research that's in the right direction.
In the quest to turn back the clock,
one of the questions that has been around for a long time is,
“how much impact do genetics have on aging?"
If my parents or grandparent lived to a ripe old age…will I?
One way to determined an answer to this question
is to take a look at how many detrimental gene variants people who live a long time have.
A “detrimental gene variant” being an inherited gene
that puts them at risk for contracting an age-related chronic disease.
Several such studies have indicated there are just as many harmful variants
in the genomes of exceptionally long-lived people as there are in the general population.
One study took a look at centenarians, exceptionally long-lived individuals, or ELLI.
These individuals are a unique segment of the population,
exhibiting unusually long lifespans and health spans.
They examined three groups of individuals:
the cohort of ELLI, their offspring, and a control group of individuals without a history of familial longevity.
And they found that the burden of pathological variants
did not differ between the three groups.
In other words, they found no evidence of a difference in detrimental gene variants
between the long-lived individuals and the control group.
The study concluded that the
“high similarity in the burden of pathogenic variation between ELLI
and individuals without familial longevity supports the notion that extension of lifespan and health span
in ELLI is not the consequence of pathogenic variant depletion,
but rather a result of other genomic, epigenomic, or potentially non-genomic properties.
It also concluded that the biggest factor in the length of human lifespan
appears to be entirely a matter of lifestyle choice,
such as environmental exposure to infectious disease, particulate air pollution, etc.
Yet another study showed that centenarians are comparatively resistant to age related disease.
Even though the human life expectancy has increased over the last couple of decades,
most individuals do not appear to be living healthy lives.
The prevalence of disease and the number of years spent living with disease has been on the rise.
In spite of this, people who live to be more than 100 years of age
appear to have a reduced risk of morbidity
and a delay in the onset of age associated chronic diseases.
Centenarians have fewer diseases, fewer limitations to performing activities of daily living,
and are less likely to be hospitalized.
In fact, most centenarians experience a compression of morbidity,
shortening of the proportion of life spent with disease and disability at the end of their lives.
Super centenarians, individuals who are 110 years old or more,
spent only 5% of their lives with age related chronic diseases,
compared to 18% in younger individuals who don’t live as long.
The older a person is, the more likely it is that a genetic risk model
will be able to correctly identify that person as someone who could live to an old age.
In individuals that were aged older than 102 years,
there was a 71% chance that these risk models could identify that person as likely to reach extreme old age,
but that chance went up to 85% in people that were older than 105.
This seems to indicate that the genetic contribution to longevity
become stronger when looking at extremely long lived individuals.
The ability to each extreme old age without any age related chronic diseases
is considered to be an extreme phenotype.
These extreme phenotypes can be useful
when trying to identify genetic variants associated with a reduced risk of disease.
The use of centenarians as extreme controls in studies involving specific chronic diseases,
has improved the ability to detect associations between genetic variants and the risk of disease.
Now, in spite of the fact that this study seems to effectively demonstrate the impact that genetics has on aging,
this study seems to agree with the previous study.
It notes that centenarians do not achieve their exceptional longevity
due to the absence of genetic variants associated with disease.
Centenarians have been found to have the same genetic variants
for increased risks of cancer, cardiac disease and neurodegenerative diseases as everybody else.
Instead it appears that centenarians are enhanced by protective genes.
These include genetic variants that are related to a reduced risk
for cardiovascular disease and hypertension, as well as enhanced immunity and metabolism.
So, while centenarians don’t appear to have any more negative gene variants than anyone else,
they do appear to have gene variants that are of a protective nature,
that will prevent them from getting age-related chronic diseases.
Good new for those of you with extremely long-lived parents or grandparents.
Hope you guys enjoyed these longevity news updates.
If you did, and you’d like to check out last month’s new, here’s a link.
And be sure to tune in next week for RAADFest News.
That’s it for me, I’m outta here.