[MUSIC PLAYING]
From a dark corner of a university laboratory
comes the device that reveals the mysteries of death!
The lifespan machine!
[LAUGHTER]
[MUSIC PLAYING]
Well, I joined the lab two and a half years ago, right
out of undergrad.
And I was brought in to run this machine
that I knew nothing about the time, called the lifespan
machine.
The lifespan machine is essentially a large distributed
microscope that allows us to observe large populations of C.
elegans simultaneously.
It's a high definition time-lapse microscopy device,
and basically what that means is,
it takes images of agar plates with worms on them, every hour,
for the entire duration of their lifespan.
C. elegans are probably the simplest complex organism
you can study.
They're full animals-- they have a pharynx, a body, muscles,
they have all the parts that you might
want to study in an animal, but they're
very small and easy to culture.
The traditional way of doing lifespan experiments
is you sit down in front of a microscope,
and you have a population of 100 to 200 animals.
And every day you go through each individual,
and you sort of poke it with a little rod, and if it moves,
it's still alive.
And it works great.
You get the experiments done, but it doesn't really
scale up that well.
Nematodes, like humans, spend the last period of their life
not really being very mobile.
So you end up seeing these old worms who can really only
move their head back and forth a little bit.
And so the task of the lifespan machine
is to detect these subtle head movements,
and then when they finally stop altogether,
you can call the animal deceased.
And now you have the full story of their lives,
before and after you do some sort of intervention to them.
The lifespan machine really starts
with individual flatbed scanners.
And then you retrofit them to turn them
into biological experiment equipment.
So you take a single scanner, And it fits 16 plates.
And each of these 16 plates can hold, let's say, 50 worms.
And then you can buy as many scanners as you want.
For certain nightmare weeks, I have run two to three incubator
experiments with as many as 15,000 worms.
We were interested in the aspect of aging
that produces a diversity of lifespan in a population.
Why some animals have different outcomes at the end of aging
as others do.
One experiment we did is we took animals
and we grew them all up at 20 degrees Centigrade,
where they're all super cool and happy and relaxed.
And then we took another population
and we put it up to 25, and another population and we
put it up to 29.
And we saw, as people have shown before, that the animals
at the higher temperatures, they lived a lot shorter.
But what we were looking at specifically,
is exactly how the shape of the distribution changed.
Whether, even though they're living shorter,
perhaps they were more or less variable
in their lifespan between individuals.
So what we saw was that the populations all
exhibited temporally rescale distributions, which
is that the variation that we see between individuals
seem to be locked in proportion with the mean lifespan.
The distribution of lifespan is merely
being stretched or compressed on a time axis.
Given the complexity of the underlying biology of aging
and the different interventions we were looking at,
I thought we would have an intervention
like a genetic change produce a very different effect
on the lifespan distribution than, say, change in diet
or a change in temperature.
And we found is that all of these changes
produced a very simple effect on the distribution of lifespan.
| think out of these lifespan distributions comes the idea
that there's a central aspect of aging that's maybe resilience
or frailty, and I think the temporal scaling
we see in lifespan distributions is driven by this resilience
or frailty.
It's very consistent with the idea
that there is one aspect of an organism that
determines its risk of death from all sorts of causes.