Gather ‘round, boys and girls, and I’ll tell you a story about mice, aging, and…blood.
Seriously, it’s not a bad story. Stick around.
In today’s story, I’m going to tell you about the research of Irina and Michael Conboy
of the University of California, Berkeley.
This husband and wife team have done some ground-breaking research
into the effects of both young and old blood on aging…in mice.
Our story begins in 2005, when the Cowboys came up with a theory:
that our bodies hold on to the ability to regenerate damaged tissue by utilizing stem cells,
in spite of growing old.
But that somehow, these stem cells get turned off as we age through changes in our biochemistry.
The idea was that by replacing broken cells and tissues with healthy ones,
the capacity to repair dysfunctional tissues in organs could be restored to youthful levels,
and that this capacity is regulated through specific chemicals which change with age
in ways that become counterproductive.
So, they pulled together a team of researchers at UC Berkeley
and this team surgically joined older mice and younger mice together.
Turned’em into conjoined twins.
When two mice are sutured together, in a technique called parabiosis,
they share not only blood, but also organs.
The old mice have access to the younger lungs, thymus, heart, liver and kidneys of the younger mice.
So the blood of the old mice is now getting filtered through these younger organs.
Now, apparently, the old blood had no effect on the young mice,
but the old mice experienced a rejuvenating effect from this technique.
Although the effects took several weeks to reach full expression,
the old mice experienced youthful muscle regeneration and improved neurogenesis in the hippocampus.
The parabiosis experiments demonstrated that old stem cells could be reactivated
and made to behave like young ones if properly stimulated.
As a result of those experiments,
media coverage seemed to fixate on the idea that young blood could reverse the aging process,
and since then, scientists have spent millions
on investigating the potential medical properties of young blood,
with a number of biomedical business ventures springing up to infuse old people with young blood.
This in spite of the fact that Conboy had said that her experiments simply showed that aging is reversible
and not set in stone,
and that infusion of young blood into the elderly is, under no circumstances, to be considered “medicine.”
In fact, she has stated that infusing your body with someone else’s blood can have severe side effects,
such as tissue rejection leading to organ failure.
She also said that there were two possible interpretations of her experiments.
The first is that rejuvenation was due to young factors in the blood that had become diminished with age,
and that when these young factors were administered to old mice, they became rejuvenated.
The other interpretation is that as we age,
there is an elevation of certain proteins or factors in the blood that become detrimental,
and that these were removed or neutralized by the organs of the young mice.
In other words, either the young blood had rejuvenating factors, or the old blood had aging factors.
Fast forward to 2016.
The Conboys designed new experiments to help them determine
which of these two interpretations might be true.
They decided to simply exchange blood between old mice and young mice, without surgically conjoining them.
And the results were a bit startling.
First, rather than taking several weeks, the effect took place immediately, within 24 hours.
And guess what?
The old mice did not experience any beneficial effects from the young blood.
They were not rejuvenated. But the young mice aged.
The young blood still circulating in the young mice could not compete with the old blood.
So the Conboys concluded that, rather than there being rejuvenating factors in young blood,
it was that there were inhibiting factors in old blood that caused aging.
They discovered that age-accumulated proteins, such as transforming growth factor beta 1, or TGF-β1,
inhibited the stem cell’s ability to repair tissues even in young mice,
and that when TGF-β1 signaling is normalized to its young levels,
old mice that are the equivalent of 80-year old people, experience youthful rejuvenation.
These experiments suggested that while young blood did appear to be beneficial to old stem cells,
the real culprit of the broad loss of tissue repair in older individuals
was the negative effects of age-accumulated proteins in aged tissues and circulation.
OK, all of this background has set the stage for the study that I really want to talk about.
In May of this year, the Conboys published their latest study in the journal called “Aging.”
In this study, the Conboys came up with the idea of performing a “neutral” blood exchange.
If the buildup of certain proteins is the primary inhibitor of tissue repair and maintenance,
this suggests an alternative, and safer path:
simply diluting the old individuals own blood, by diluting the blood plasma, along with the aging factors.
So the research team drew blood from both young and old mice, separated out the plasma,
and then diluted that plasma by swapping half of the plasma with saline and albumin.
The albumin simply replaced albumin that was lost when half of the plasma was removed.
They then infused this diluted plasma back into the animals that it had been drawn from,
young diluted plasma back into young mice and old diluted plasma back into old mice.
Now, if the young diluted plasma made the young animals grow old,
it meant that diluting the young factors in the young mice’s blood
prevented those factors from doing their job.
But if the old diluted plasma made the old mice young again,
it meant that much of the inhibiting factors had been removed from their blood,
stopping those factors from inhibiting the repair and maintenance processes
and restoring the mice to youthful levels.
And that’s what happened.
The diluted young plasma had no effect on the young mice.
But the diluted old plasma had rejuvenating effects on the old mice
that actually exceeded the effects of the young blood from the original, 2005 experiments.
So they did what’s called a “proteomic” analysis of the blood plasma
to determine how proteins in the blood changed following the procedure.
And the analysis showed that there was a lower concentration of pro-inflammatory proteins
that become more elevated the older we get.
It also revealed a molecular re-setting of the systemic signaling environment,
elevating the levels of proteins which regulate tissue maintenance and repair
and promote immune responses.
Now, this type of procedure already exists for humans.
It’s called therapeutic plasma exchange, or plasmapheresis, and it’s FDA-approved.
It’s been used to treat a variety of autoimmune diseases.
So, I guess that the conclusions that one can draw from all of this
is that there are certain proteins that can accumulate as we age,
inhibiting the stem cells from doing necessary maintenance and repair.
By diluting these proteins in the blood, we can allow the stem cells to do their works,
restoring repair functions to youthful levels.
These experiments do not mean that this techniques are ready to be used or well understood.
This needs a lot more research, but it's pretty clear that the future of antiaging in general,
and plasma dilution in particular, looks very promising.
Hope you guys enjoy this video.
If you'd like some more information on theories about achieving longevity,
check out this playlist on the Hallmarks of Aging.
That's it for me, I'm outta here.
Catch ya next week.