Animals that defy the rules of aging help scientists study longevity

Neil Bromhall/Shutterstock

• Some long-living animals seem to defy the
  rules of aging, so scientists are studying them.
• Two animals of interest to researchers are the naked
  mole rat, which lives decades longer than its rodent relatives,
  and turtles, which can live up to 200 years. 
• Researchers have found noticeable differences in the
  ways these animals’
  metabolisms and
  mitochondria function. 

---

Being a freak of nature isn’t always a bad thing, especially if
you defy the conventions of
aging. 

Naked
mole rats and
turtles are outliers when it comes to the rules of nature.
The mole rat lives up to 31 years, decades longer than its other
rodent relatives. Turtles are one of the longest-living creatures
on Earth. 

Comparing the biology of these
animals to others that age poorly provides valuable insights to
scientists about which biological pathways are most important for
longevity. That information could ultimately help
them find ways to increase human lifespans. 

A cornucopia of factors are at play as a younger organism gets
older: proteins get damaged, they build up and disrupt cell
functions, mutations occur, and once-harmless cells turn
into cancer. But the
important question when it comes to aging is not how it happens,
according to Richard Miller, director of the Glenn Center of Aging
Research at the University of Michigan.

“The real question is what has
been done across species or within a species to slow
it,” Miller told Business Insider.

Long live the naked mole rat

A popular theory in the field
of aging is that an organism puts most of its resources —
such as nutrients, energy, time and effort — either into maintaining
their body or reproducing, but not both. In people, for
example, women’s average lifespan decreases if they
have children. Scientists believe this happens
because human reproduction can cause damage to cells and
deplete resources in the body that would otherwise have been used
for cellular repair.

But paradoxically, breeding seems
to extend the life of the naked mole rat. 

Scientists Martin Bens and Alessandro Ori at the The Leibniz
Institute on Aging in Germany are working to
understand this anomaly. 

Each colony of mole rats designates a
queen, the same way ants do, and only she breeds and bears
young. There is also only one breeding male per colony. But
non-breeders can transition to become a breeder, so Bens
and Ori studied that transition process. 

Their results suggested that the signal pathways involved
in mole rats’ transition to breeding are also involved in their
aging process.

In males, some of these
overlapping pathways are related to their metabolism, the process
of converting food to usable units of energy in the body.
Scientists found that breeding male mole rats produced
greater-than-normal amounts of energy in their testes cells, and
lower-than-normal amounts in their skin cells. Diverting energy
in this way could play a role in delaying the aging
process. 

Brandon
Vick, University of Rochester

Ori and Bens also observed
differences in the composition of the mole
rats’ mitochondria:
the small organelles in cells that power metabolic processes.
They observed that the naked mole
rats had a reduced mitochondria respiration rate compared to
guinea pigs, which meant that the mole rats were making less
energy and using less fuel and oxygen.

The researchers also found that
all the naked mole rats preferred to use lipids or fats as an
energy source, rather than the carbohydrates or sugars that
shorter-lived rodents mostly use. 

Another factor that allows naked
mole rats to live so long is their abnormally low body
temperature. Lower
basal body temperatures in animals are usually correlated
with prolonged healthspan, and naked mole rats are mammals but
aren’t warm-blooded, which makes them an anomaly in the rodent
family.

Finally, Ori and Bens examined
naked mole rats’ livers. Livers generally detoxify the body and
eliminate chemicals that can damage cells and accelerate aging.
In mole rats, these detox pathways were more active
than the same systems in guinea pigs, suggesting that mole
rats keep their cells healthy and undamaged from toxins more
efficiently. That could also explain why they out-live their
rodent cousins.

The tortoise and the human

Tortoises and turtles are masters
of aging. Jonathan, a Seychelles giant tortoise, is the oldest
known terrestrial animal at 186 years of age, and is going
strong.

“There are tortoises until
recently that knew Darwin personally,” Kenneth Storey, a
professor at Carleton University who studies turtles, told
Business Insider.

These ancient beings are the most
evolved and complex animal that can survive complete anoxia: a
total absence of oxygen. 
Turtles can go well over a year without
oxygen.

By comparison, naked mole rats
can survive almost 20 minutes without oxygen, and oxygen-deprived
humans only get about two minutes of brain activity and five
minutes of heart activity before all systems shut down and organs
become irreparably damaged.

To live without oxygen, Storey
said, turtles drop their metabolism rate to next to
nothing. 

“What the turtles do is in a
tissue-specific manner, shut down genes and sub-cellular
organelles that use energy or that need maintenance,” he
said.

A
giant green turtle rests on a coral reef in the Celebes Sea,
November 7, 2005.
Reuters

Turtles shut their energy
production off by changing an enzyme called pyruvate
dehydrogenase, which turns off their mitochondria.
Starving the mitochondria then
forces the turtle’s body to secrete a special protein
that protects cells. 

In the absence of oxygen, turtles can initiate an organized shutdown of
50,000 processes in their bodies.

“We know what happens to the
pathways and we know what happens to the system, but we don’t
know what ultimately controls it,” Storey said.

He added that under stressful, low-oxygen conditions, turtles’
bodies do one other thing exceptionally well: “They don’t panic.”

In these circumstances, turtles
turn off most of their stress-response proteins so they can focus
what little energy they have on reshaping their cells to
operate differently in anoxic conditions. Those changes include
preventing cells from digesting and turning over proteins, a
process called autophagy that can make detritus and cause
damage. Limiting the amount of matter created and destroyed
in their bodies allows turtles to maintain a pristine internal
balance. 

By comparison, human cells that
are deprived of oxygen turn on stress kinases: signaling proteins
that help facilitate communication in the body in order to
respond to a challenging situation. Over-activating stress
kinases can use up a lot of energy, overload the system, and
ultimately trigger cell death.

When juxtaposing humans and
turtles, Storey thinks longevity depends on an energy
trade-off.

“Think of these lower animals as
living longer than us because their pilot light is lower. They’re
not 37 degrees [Celsius], they’re not racing around,” he
said. 
“They’re not
burning the candle at both ends, they’re barely burning the
candle at one end, and during anoxia they stop burning the
candle. That’s how they can live so long. It’s a pace
argument.”

All about energy

The idea that metabolism is one
of the key factors in the aging process has been a cornerstone of
many studies on aging. Hypothetically, if you turned down the
energy production in your cells, you could live longer and get
fewer wrinkles, Storey said. But you would probably not have
enough energy to sustain a normal human life.

Humans’ complexities mean we
require more energy and a constant supply of oxygen to power our
cells. We also need to consume food frequently to fuel our bodily
functions.

“What we’ve opted for is a high
velocity lifestyle, which ties us in to oxygen all the time,”
Storey said. 

Rozalyn Anderson, an associate
professor at the University of Wisconsin School of Medicine and
Public Health, told Business Insider that it’s hard to
ignore how big a role metabolism and energy balance play in
aging. Anderson studies
caloric restriction in
 monkeys, and said evidence is starting
to show that age-related diseases show up with increased
prevalence in people who have metabolic issues and
obesity.

“I think it’s all about energy:
energy use, energy storage, and the type of pathways that are
being engaged to derive energy,” Anderson said.