The last decade might one day be remembered as the beginning of the life extension equivalent
of the Renaissance—an age when life extension research flourished,
filled with optimism about the feasibility of humanity's oldest dream:
to be free from aging and remove the cap that it imposes on the duration of our lives.
Whether this will actually pan out remains to be seen; while today, for the first time in history,
we have the scientific knowledge to actually research potential means of rejuvenation,
it's not yet clear when such research will lead to successful therapies in humans.
While we wait to see how events will unfold and if aging is indeed on its way out,
let's take a brief look back and see how we got to where we stand today.
Dreams of longevity, eternal youth, and even eternal life are almost as old as humanity;
the fountain of youth, a mythical spring whose waters were able to rejuvenate those who drank
or bathed in them, is something that everybody has heard about, and one of the oldest mentions of it
was in the third book of the ancient Greek historian Herodotus.
The fountain of youth is hardly the only myth about overcoming aging;
for example, one of humanity's most ancient works of literature, the Epic of Gilgamesh,
revolves around the journey that King Gilgamesh undertook to find the legendary flower of rejuvenation.
Other stories, such as that of the Greek warrior Tithonus, have a bit of a more cautionary
flavor and warn about the perils of longevity per se.
Tithonus was made immortal by Zeus, and that was great,
except he didn't make him also eternally young, with, er, less than desirable results.
The wish to overcome not just aging but also death is a central theme of religions present and past,
which, in most cases, include beliefs in an afterlife of some sort,
the existence of an immortal quality that is the prerogative of human beings, a.k.a. a soul,
resurrection, and so on.
However, not everyone throughout history was content with the promise of a life after death,
so there has been no shortage of rather… original attempts at conquering death that,
more often than not, resulted in the exact opposite.
Some sources state that gunpowder was initially conceived as an elixir of life,
and allegedly, Chinese emperor Qin Shi Huang died of mercury poisoning after taking mercury pills that
his physicians thought would make him immortal for some reason.
Things didn't really get serious until modern science arrived on the scene, and around the
second half of the 1800s, enthusiasm started to spread about the possibility of treating aging.
This enthusiasm was rather premature—after all, over 100 years later, we haven't quite defeated aging yet.
But it was at about this time that modern life extensionism was born.
Different hypotheses about what causes us to age and possible remedies were suggested
by different scientists of the time, including Elie Metchnikoff, who is credited with coining
the term "gerontology"—the science that studies the underlying causes of aging.
Metchnikoff was a pioneering immunologist who received a Nobel Prize in 1908 for his discovery of phagocytosis,
the cell's ability to engulf foreign bodies, which plays a central role in immune defense;
he thought aging was a disease no different from any other and that it should be treated as such.
In Metchnikoff's view, aging resulted from a constant struggle between functional and harmful tissues,
an ongoing conflict between degenerative and regenerative processes;
he thought phagocytes could be major drivers of aging, as well as toxin-producing intestinal
bacteria, which wasn't too far off the mark, given that, to the best of our knowledge,
chronic inflammation and gut microbiome activity do play a role in aging.
A number of other hypotheses were put forward during that time, and if you're interested
in the details, you can find more sources in the description below.
Right now, we're going to fast-forward to the last few decades, when things got really interesting.
One of the first mindset shifts in the field of aging research came with Leonard Hayflick's
discovery that vertebrate cells have only a limited potential for replication.
Prior to that, it was believed that cells can go on dividing indefinitely.
What Hayflick found out was that cells in his culture slowed down and eventually stopped
replicating after around 50 replications.
This phenomenon, which Hayflick named "senescence", was further observed by other scientists,
who managed to reproduce his results several times; when he published his discovery in 1965,
Hayflick hypothesized a connection with aging.
This reproduction limit is now universally known as the Hayflick limit.
Replicative senescence was eventually correlated to another cellular phenomenon: telomere shortening.
Scientists observed that, as replication slows down, the protective caps at the end of the
chromosomes of each new generation of cells become progressively shorter,
and once they disappear altogether, senescence sets in.
However, it was known that at least some cells are capable of unlimited proliferation,
such as stem cells and cancer cells, so it seemed reasonable that there should be a way around
telomere shortening; the "way around" was first theorized by Alexey Olovnikov in 1973,
and it would eventually be discovered in the form of the enzyme telomerase,
whose role is precisely that of rebuilding shortened telomeres.
In 1984, Carol Greider and Elizabeth Blackburn discovered telomerase in a small protozoan called
Tetrahymena, and this earned them a Nobel Prize in 2009.
Eventually, telomerase was discovered in human cells too,
and its composition was determinedin the late 2000s.
For a while, telomeres and telomerase were, and still kind of are,
the pop-science explanation for human aging,
and while evidence suggests they do play a role, it also suggests that
the whole picture is much larger and that there isn't a single factor causing us to age.
The late 90s saw the beginning of the true change in aging research that we're experiencing today.
In 1999, the Buck Institute for Aging Research in Novato, California was inaugurated,
and it has been one of the driving forces of this field of science for twenty years now.
However, despite previous research and the enthusiasm that scientists had back in the days of Metchnikoff,
when the Buck set up shop, aging research was considered an exploratory field at best,
and the idea that it could ever be a translational field was heretical.
Suggesting that it might be possible to intervene against aging was granted to get you frowned
upon at the very least, and it could even jeopardize your career as a researcher.
That's just about the time when one of the most famous names in the field, Aubrey de Grey,
started getting as frowned-upon as one could possibly be.
After he took up the study of biology, he was awarded a PhD by Cambridge for his 1999 book,
The Mitochondrial Free Radical Theory of Aging.
In the early 2000s, de Grey conceived what he then went on calling SENS, the Strategies
for Engineered Negligible Senescence—in a nutshell, the idea that periodically repairing
the body from seven different kinds of damage might be the way to go about aging,
which he described in his 2007 book Ending Aging.
To put it mildly, the idea was first dismissed as a pseudoscientific, impossible fantasy.
De Grey has always been more than convinced that his categorization of the damages of
aging was exhaustive and that SENS would work, so, despite the fierce opposition, he persisted
and went on to co-found the Methuselah Foundation.
This foundation still exists today and has collaborated with different universities and organizations,
including NASA, to speed up breakthroughs in regenerative medicine and
rejuvenation biotechnologies; it was the first organization to push the SENS repair approach,
and even though it still supports the idea, Methuselah spun out SENS Research Foundation
in 2009 specifically to focus on SENS-related research.
In time, the SENS approach became a little more appreciated; several important names
of science joined the SENS Research Foundation's advisory board, and the Foundation itself
has become known for financing cutting-edge, high-risk, high-reward basic research,
collaborating with important universities and organizations, including the Buck Institute,
which hosted one of several SENS Research Foundation conferences.
The year 2013 marked what might be a historical milestone;
the journal Cell published The Hallmarks of Aging,
in which the authors propose nine intertwined processes that might lie at the core of aging itself.
The review was somewhat reinvigorating for SENS,
as the Hallmarks categories share many common points with it,
although there are some differences that we may discuss further in future episodes.
The Hallmarks went on being one of the most cited papers of the decade, being cited by
other papers an average of almost twice daily in the past six years; this paper is one of
the main reasons why so many scientists are more optimistic and open about attacking aging,
even though we would hardly stand where we are today without the persistence of SENS
Research Foundation and the people behind it.
2014 is our own landmark year; that's when the Life Extension Advocacy Foundation was created,
along with the crowdfunding platform Lifespan.io, and we're proud to say that,
during the brief time we've existed, we've contributed to aging research in our own small way,
not just by spreading awareness on the problem of aging and advocating for rejuvenation
but also by crowdfunding research.
Over the last few years, many things have changed, and a lot of progress has been made.
For example, the first project Lifespan.io crowdfunded was MitoSENS, a proposed way to
address the hallmark of mitochondrial dysfunction, which resulted in a successful proof-of-concept
experiment and a paper that we will certainly talk about in a future episode.
Epigenetic clocks—a set of tools for assessing biological age—have been introduced and refined;
senolytics, drugs that address cellular senescence,
have worked wonders in mice and have been tested in humans;
stem cell treatments have continued to advance;
there have been human trials on regenerating the thymus, a central organ to the immune system that starts
failing quite early on in life; and there are many more interventions being explored
by a great many biotechnology companies.
Our short journey into life extension history is over; right now, all we can do is work
hard to make sure that historical accounts from the near future will include the date
when the final nail was put into the coffin
of aging.
Keep in mind that this account of life extension history was extremely brief and incomplete,
otherwise this would be an excruciatingly long video,
but it's also because we're a small team with far too many things to do;
if you'd like, you could help solve that problem
by becoming a Lifespan Hero at lifespan.io/hero or maybe even working with us;
check the description below to find more information about that.
