Flipping a genetic switch for longer lifespans

The research looked to explain why stressing the mitochondria of nematode worms during early development nearly doubles their lifespan

Scientists have successfully identified epigenetic modifiers with strong links to metabolism and lifespan. Discovered in worms and observed in mice, it's possible that the enzymes could provide a pathway to longer life, effectively switching on a set of genes at an early age.

Given the universal appeal of living longer, it's not surprising that a lot of research time and money goes into finding ways to potentially increase human lifespans. We've seen some interesting work taking on the topic recently, with Mayo Clinic researchers getting positive results in mice from clearing out damaged cells, extending their lives by up to an impressive 35 percent. The new research tackles things on a slightly deeper level, pinpointing a means of essentially "switching on" longer life.

We've known for decades that there's a correlation between the availability of nutrients during early development, and adult health and metabolism. Even short-lived changes in diet, which directly affects how much energy is available to cells, can induce lasting changes in an organism.

With that knowledge in mind, the researchers decided to investigate the idea that reducing the energy production of cells might slow the ageing process. They looked to a small window of development in which such changes are known to have the biggest impact, focusing their investigations on mitochondria, which are the power stations of cells.

Though tiny, mitochondria have a huge impact on health, with malfunctions thought to play a role in the vast majority of diseases in which age is a key factor, such as Parkinson's, Alzheimer's and cancer.

A slightly more recent discovery, made by the University of California, Berkeley's (UC Berkeley) Professor Andrew Dillin in 2004, showed that stressing the mitochondria of worms during early development nearly doubles their lifespan. With the new work, which is a collaboration between UC Berkeley and Switzerland's École Polytechnique Fédérale de Lausanne (EPFL), the researchers have been unravelling exactly how this mechanism actually works.

What they discovered is that the mitochondrial stress flips a sort of genetic switch, activating enzymes in the brain that act on DNA, exposing some 1,500 genes that affect how the mitochondria function. A second set of enzymes are also activated, tagging the genes and effectively ensuring they're active for most of, if not the entirety of the animal's life.

This has the effect of altering the brain's sense of hunger, affecting neurons that sense the nutritional status of the animal, and causing them to trigger a change in metabolism.

Observations of inbred laboratory mice supported the notion that the identified enzymes play a big role in prolonging life. The team found that the mice that lived longer (significantly so in many cases) were those with higher expression of the identified enzymes.

"Two of the enzymes we discovered are highly, highly correlated with lifespan; it is the biggest genetic correlation that has ever been found for lifespan in mice, and they're both naturally occurring variants," said Professor Dillin.

How do these findings relate to human lifespan? Well, right now we're still putting together pieces of a very complex puzzle, and it's possible that these mechanisms could be notably different in humans.

That said, the breakthrough is significant, and it is possible that the knowledge might lead to an ability, somewhere down the line, to boost the identified enzymes, reprogramming our metabolisms to improve health, and just maybe, just maybe, lengthen our lifespans.

Full details of the study are published online in the journal Cell.

Source: UC Berkeley

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