“We are on the cusp of curing aging.”
Those are the words of molecular biologist Dr. William
Andrews, founder and CEO of Sierra Sciences, a company with the stated goal
to “cure aging or die trying.” In the quote above, which comes from a September 2010 Sierra Sciences press release, Andrews is referring to a nutraceutical (i.e., a natural
food-derived product meant to provide health or medical benefits, like
vitamin C or folic acid) that his company discovered, known as TA-65. It
supposedly slows down the aging process in humans by activating an enzyme
called telomerase.
Telomerase acts on telomeres—simple repeating sequences
of nucleotides (the building blocks of DNA) found at the tips of chromosomes
that are important to cell division and replication. Cells must replicate
their genes accurately and completely whenever they divide, or the so-called
daughter cell will malfunction and die. However, most DNA polymerases (the
enzymes that replicate DNA) cannot copy chromosomes all the way to the end. Thus,
during each cell division, a small region at the tip of the chromosome (part
of the telomere) remains uncopied.
So, the telomeres have a crucial function: they act as a buffer zone
during cell division, protecting the genes in the chromosome and ensuring
that they fully replicate. But there’s a cost: successive divisions cause the
telomeres to erode over time.
When telomeres erode away, parts of critical genes remain uncopied,
eventually spelling death for the cell. Some scientists think that this
telomere erosion is what imposes a limit on our lifespans and causes our
health to decline as we age; they also think that an answer to this dilemma
might be telomerase activation.
Telomerase combats telomere erosion by adding telomeric subunits
(repeating sequences of nucleotides) to the ends of the chromosome, thereby
allowing it to continue to divide intact. The origin of telomerase still
remains a mystery. It appears to be critical during human embryonic development,
but then fades away. Little is found in the body after birth, for reasons we
don’t yet understand.
Some scientists, like Dr. Andrews, think telomerase activation could be
the cure for aging that his company is looking for, and he views TA-65 as a
potential big first step in that direction. According to Andrews:
TA-65 is going to go down in history as the first supplement you can take
that doesn’t merely extend your life a few years by improving your health,
but actually affects the underlying mechanisms of aging. Better telomerase
inducers will be developed in the coming years, but TA-65 is the first of a
whole new family of telomerase-activating therapies that could eventually
keep us young and healthy forever.
Well, if proven true, that’s a game-changer, to say the least. Just keep
on living until you meet with a fatal accident. Woo hoo! But… hold on. Turns
out we shouldn’t get irrationally exuberant just yet. It might not be such a
good idea to activate telomerase, after all—because of the role it seems to
play in cancer.
Cancers can arise when genetic mutations inside a cell cause it to escape
from normal controls on replication and migration. The cell and its offspring
multiply uncontrollably while invading and damaging nearby tissue. With the
presence of telomerase, cancerous cells—which apparently synthesize the
enzyme—avoid telomere erosion. They essentially become immortal, dividing for
as long as the host survives. A 2012 study by the MD Anderson Cancer Center
found that activating telomerase following telomere degradation actually made
tumors stronger and more deadly.
So alas, TA-65 and telomerase activation might not be the miracle aging
“cure” Dr. Andrews was hoping for. But what about other areas of
anti-aging/longevity research?
There’s a lot of talk these days about humans becoming essentially
immortal in the near future, but is the hype supported by any actual
research? Let’s see.
The Quest for Immortality Continues
People have been obsessed with the idea of immortality and living forever
for centuries. According to Adam Gollner in The Book of Immortality: The
Science, Belief, and Magic Behind Living Forever:
The twenty-five-year old Emperor Ai of Jin died in 365 CE, after
overdosing on longevity drugs. He wasn’t the last leader to die trying to
live forever. The fascination with chemical immortality reached an ironic
apogee centuries later, during the T’ang dynasty (618-907 CE), when elixirs
poisoned those hoping for precisely the opposite effect.
In the late 1300s, legend has it that alchemist Nicolas Flamel created a
“sorcerer’s stone” that was then used to produce a potion, the elixir of
life, which is said to make the drinker immortal. The idea was so alluring that
despite a complete lack of evidence to support the existence of the stone and
the elixir, other scientists, including the great Sir Isaac Newton, later
tried to replicate Flamel’s results. To no avail. And of course there’s the
fabled Fountain of Youth that became associated with Spanish explorer Ponce
de León in the early 1500s. We know what happened to him.
People today are no different. Not wanting to die is as natural as life
itself. Below we’ll present a few interesting discoveries that may (or may
not) mark some progress in our quest to live forever. But first we must
answer a question.
What Is Anti-Aging Medicine?
The telomere erosion we talked about earlier certainly plays a part in
aging, but most scientists don’t believe that it’s the only factor. They
typically view aging as a sort of ongoing cellular wear and tear, where
stresses from the environment and inside our cells (such as errors in DNA
replication) accumulate throughout life and eventually wear out our cells and
tissues.
Scientists who search for a modern anti-aging elixir seek to slow down or
reverse this process in order to extend both the maximum and average lifespan
of people. And even if that doesn’t pan out, advocates of anti-aging medicine
contend that at the least, targeting and altering the underlying mechanisms
of aging will bring us more efficient ways to deal with age-related
conditions like heart disease and many cancers.
Now critics dispute the portrayal of aging itself as a disease, of course,
but that’s not for us to debate here. Let’s just agree with the commonly
stated goal of anti-aging medicine, to “add more years to your life, and life
to your years.”
Caloric Restriction Mimetics
In 1934, scientists at Cornell University found that mice on an abnormally
low-calorie diet lived about twice as long as mice who ate as much as they
wanted. Scientists have since found that this caloric restriction also
lengthens the lives of fruit flies, rats, and even primates, suggesting that
this is an avenue worth pursuing in anti-aging medicine.
The going (very basic) hypothesis of why these animals live longer is that
their bodies treat food scarcity as an extreme type of stress. So they mount
a physiological response to cope with the lack of nutrition. And that
toughens them up, promoting health and longevity during the time of
deprivation, even if that time is significantly extended.
Starving yourself in order to get stronger? That sure seems
counterintuitive. But the results from numerous experiments make a compelling
case.
The problem with caloric restriction is that it’s not a very pleasant way
to live if you’re fortunate enough to be able to consume a “normal” amount of
food on a regular basis (which is between 2,400 and 3,000 calories a day for
active males). So scientists are trying to develop drugs (called caloric
restriction mimetic drugs) that re-create the anti-aging benefits of caloric
restriction without having to change one’s diet.
Resveratrol, which is found in the skin of red grapes, was an early
favorite in this category. It was first thought to activate a class of
enzymes called sirtuins that have been associated with the anti-aging
benefits of caloric restriction; but more recent studies have raised serious
doubts about whether this compound (and more potent versions of it) actually
activates these enzymes and has life-extending benefits.
A drug called rapamycin has shown more promise as a caloric restriction
mimetic by inhibiting a molecular signaling pathway called TOR. The TOR pathway
acts as sort of as a food sensor and helps regulate the body’s response to
nutrient availability. Blocking it has been shown on multiple occasions to
extend the lifespan of lab knockout mice while keeping them lean and healthy
in their later years. Unfortunately, however, the drug’s anti-aging potential
in humans is offset by its potent immunosuppressant effects.
Overall, research in this field has a long way to go.
NAD
As we noted above, aging is a sort of cellular wear and tear. According to
Dr. David Sinclair of Harvard Medical School, there’s a specific biological
signal that accompanies aging and tells cells it’s time to check out. It’s
triggered when the cell perceives a lack of oxygen. That makes the
mitochondria less efficient at converting fuel (such as glucose) into the ATP
needed for cells to function properly.
But Sinclair and his colleagues recently found a way to counteract that
signal. Using a natural chemical compound called NAD, they were able to
revive older cells in mice and make them appear energetic and young again.
After receiving NAD for just one week, two-year-old mice tissue came to
resemble that of six-month-old mice. “When we give the molecule, the cells
think oxygen levels are normal and everything revs back up again,” Sinclair
explained. “If a body is slowly falling apart and losing the ability to
regulate itself effectively, we can get it back on track to what it was in
its 20s and 30s.”
Let’s hope.
FOXO
Molecular biologist Cynthia Kenyon thinks she may have found another of
the keys to a long life through her study of tiny worms called C. elegans.
By tweaking just one gene in these worms (to simply make it more active), she
was able to take two-week-old C. elegans (which is a creaky old age
for these things) and make them appear about half that age. And her modified
worms lived twice as long as the normal worms. “So they’re like 90-year-old
people who look 45,” said Kenyon. The gene Kenyon changed: FOXO. FOXO is a
sort of master gene that helps C. elegans protect and repair its
tissues (and live longer) by controlling a number of other genes.
According to Kenyon:
You can think of it as a superintendent of a building. So
if you have a building, a nice big building, obviously it has to be
maintained. What FOXO does, or the building superintendent does, is to keep
the building in good working order. It makes sure that the walls are painted,
by hiring painters; it makes sure that the floors are swept. The building
superintendent would hire workers to do these different things. What
FOXO does, in the cell, is it switches on other genes … I’d say, altogether,
there are probably about a hundred worker genes that have very important
roles. And, together, what you get is a cell or tissue or an animal that
stays in really good working condition for a lot longer.
What’s particularly exciting about Kenyon’s work is that the FOXO gene is
also found in humans, and that a more protective version of FOXO (as in
Kenyon’s modified worms) is associated with longer, healthier lives. Molecular
biologist Timothy Donlon found in his studies that if you have this more
protective version of FOXO, you have a twofold greater chance of living to
100. And if you have two copies of it, you have a threefold greater chance of
living to 100, while remaining healthy. So the gene is indeed associated with
adding life to your years and years to your life.
If scientists could create a drug to tweak FOXO in humans like Kenyon did
in her worms, it seems like we’d have an effective anti-aging medicine on our
hands.
We could go on with other examples of promising research in anti-aging
medicine, but that’s a reasonable sample. It’s the ultimate area of
scientific research, really. Moreover, it seems likely to bring benefits to
humankind (and also be lucrative for savvy investors) whether aging is a
disease that can be “cured” or not.
And before leaving you today, I do want to remind you once more about the
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