The key to a longer life? How much genes express themselves

  • Two regulatory systems controlling gene expression appear to be critical to the length of our lifespan, according to biologists at the University of Rochester.
  • Long-lived species tend to have low expression of genes involved in energy metabolism and inflammation, and high expression of genes involved in DNA repair and RNA transport.
  • Healthy sleep schedules and avoiding exposure to light at night could boost our lifespan by reducing the expression of genes involved in energy metabolism and inflammation.

Natural selection has produced mammals that age at dramatically different rates. Take, for example, naked mole rats and mice. The former can live up to 41 years, nearly ten times as long as similar-size rodents such as mice.

What accounts for longer lifespan? According to the new research from biologists at the University of Rochester, a key piece of the puzzle lies in the mechanisms that regulate gene expression.

In a paper in Cell Metabolism, the researchers investigated genes connected to lifespan. Their research uncovered specific characteristics of these genes and revealed that two regulatory systems controlling gene expression—circadian and pluripotency networks—are critical to longevity.

The findings have implications both in understanding how longevity evolves and in providing new targets to combat aging and age-related diseases.

Alzheimer’s Diesease, a result of rapid aging that causes dementia, is a growing concern. Dementia, the seventh leading cause of death worldwide, cost the world $1.25 trillion in 2018, and affected about 50 million people in 2019. Without major breakthroughs, the number of people affected will triple by 2050, to 152 million.

To catalyze the fight against Alzheimer’s, the World Economic Forum is partnering with the Global CEO Initiative (CEOi) to form a coalition of public and private stakeholders – including pharmaceutical manufacturers, biotech companies, governments, international organizations, foundations and research agencies.


The initiative aims to advance pre-clinical research to advance the understanding of the disease, attract more capital by lowering the risks to investment in biomarkers, develop standing clinical trial platforms, and advance healthcare system readiness in the fields of detection, diagnosis, infrastructure and access.

The researchers compared the gene expression patterns of 26 mammalian species with diverse maximum lifespans, from two years (shrews) to 41 years (naked mole rats). They identified thousands of genes related to a species’ maximum lifespan that were either positively or negatively correlated with longevity.

They found that long-lived species tend to have low expression of genes involved in energy metabolism and inflammation; and high expression of genes involved in DNA repair, RNA transport, and organization of cellular skeleton (or microtubules).

Previous work from the researchers has shown that features such as more efficient DNA repair and a weaker inflammatory response are characteristic of mammals with long lifespans.

The opposite was true for short-lived species, which tended to have high expression of genes involved in energy metabolism and inflammation and low expression of genes involved in DNA repair, RNA transport, and microtubule organism.

When the researchers analyzed the mechanisms that regulate expression of these genes, they found two major systems at play. The negative lifespan genes—those involved in energy metabolism and inflammation—are controlled by circadian networks. That is, their expression is limited to a particular time of day, which may help limit the overall expression of the genes in long-lived species.

This means we can exercise at least some control over the negative lifespan genes.

“To live longer, we have to maintain healthy sleep schedules and avoid exposure to light at night as it may increase the expression of the negative lifespan genes,” says Vera Gorbunova, professor of biology and medicine at the University of Rochester.

On the other hand, positive lifespan genes—those involved in DNA repair, RNA transport, and microtubules—are controlled by what is called the pluripotency network. The pluripotency network is involved in reprogramming somatic cells—any cells that are not reproductive cells—into embryonic cells, which can more readily rejuvenate and regenerate, by repackaging DNA that becomes disorganized as we age.

“We discovered that evolution has activated the pluripotency network to achieve longer lifespan,” Gorbunova says.

The pluripotency network and its relationship to positive lifespan genes is therefore “an important finding for understanding how longevity evolves,” says Andrei Seluanov, professor of biology and medicine.

“Furthermore, it can pave the way for new antiaging interventions that activate the key positive lifespan genes,” Seluanov says. “We would expect that successful antiaging interventions would include increasing the expression of the positive lifespan genes and decreasing the expression of negative lifespan genes.”


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