Welcome back to the Immortals Club.
We’ll start off today with--
Everyone!
Everyone, look!
C. elegans – a new member of The Immortals?
C. elegans?
Caenorhabditis elegans!
They’re nematodes – microscopic worms that geneticists like to use because of their
short generation times and small genome.
They’re also self-fertilising hermaphrodites, which makes mutations and inbreeding much
easier.
Ah yes, you were a scientist in your past life, weren’t you?
That’s right!
For centuries, humans have searched fruitlessly for ways to prevent aging, but now it seems
like they’ve finally found a clue – and it’s all thanks to the amazing field of
genetics!
How exciting!
Exciting?
Worms becoming immortal?
Well, they haven’t actually reached immortality yet.
See, aging is arguably one of the least understood aspects in biology.
The first instance of lifespan extension was seen only 40 years ago by Michael Klass, who
screened C. elegans mutants that live longer than wild-type – and even then, he thought
it was because of their restricted diet!
It was Thomas Johnson who showed that this life extension was due to a mutated gene,
which was aptly named age-1.
Only a decade later, Cynthia Kenyon found a second gene involved with aging – the
daf-2 gene.
This is essential for dauer formation, which is an alternate, long-lived state that C.
elegans use to survive stressful conditions.
Kenyon actually called daf-2 the “grim reaper gene”.
Oh?
Yeah, because she found that inducing a loss-of-function mutation could double the lifespan of C. elegans!
These mutants also appeared as healthy as age-matched wild-type adults.
Excellent question, zombie!
In fact, that was exactly what Kenyon’s study in this article was trying to answer!
Previously, they discovered that daf-2 mutants require two downstream genes for extended
lifespans – daf-16 and daf-18, both of which are transcription factors.
So, if age-1 acts in the same pathway as daf-2, mutations in daf-16 and daf-18 should also
suppress the longevity of age-1 mutants.
To test this, they needed both daf-16; age-1 double mutants and daf-18; age-1 double mutants.
Kenyon exploited the hermaphroditic behaviour of C. elegans to create these; crossing age-1
mutant hermaphrodites with daf-16 and daf-18 mutant males respectively.
The F2 progeny were then chosen based on their phenotype, and genetic markers linked to those
two genes were used to confirm this.
By measuring their lifespans, they found that daf-16 and daf-18 double mutants had similar
mean lifespans to wild-type, whereas age-1 mutants had around double their lifespan – similar
to daf-2!
However, it should be noted that to create age-1 mutants, a fer-15 mutation was needed
and present in all mutants.
So, lifespan extension might have been due to fer-15, not age-1.
Nonetheless, the results demonstrate that proper function of both daf-16 and daf-18
is required for longevity in age-1 mutants.
This also suggested that recessive mutations in age-1 and daf-2 work in tandem to increase
lifespan for C. elegans – although not in an additive way, as they found that age-1;
daf-2 double mutants had the same lifespans as daf-2 mutants.
Okay, so those genes help extend lifespan in C. elegans, but what about other animals?
Well, subsequent studies found that fruit flies, mice, and even humans have orthologs
to both daf-2 and age-1 – namely, insulin-like growth receptor and phosphoinositide 3-kinase.
This provided evidence of aging being controlled by a hormonal pathway – which makes sense,
given the various hormonal changes that occur from adolescence to adulthood.
Furthermore, the results from these studies have been used for research into treatments
against progressive diseases like cancer – specifically targeting the IGF-1 and P13K pathways.
Unfortunately, despite the influx of research, humans haven’t quite reached the stage of
preventing aging all together.
So, no, despite what the headline suggests, we probably won’t be getting new members
right now.
Aww.
But hey guys, we’re immortals!
We can wait another century or two – besides, with the rate at which science is advancing,
we might even see both C. elegans and humans here at the Immortals club sooner rather than
later!
Yay, new members!
What did you work on before you died anyway?
Oh, just some small experiments on pea plants, nothing special.
Huh.