Scientists reverse ageing, extend life in mice

Washington, December 16

Scientists have successfully increased the lifespan of mice by reprogramming their body's cells using a breakthrough technique that may lead to new therapeutic approaches for improving human health and longevity.

Researchers at the Salk Institute in the US have found that intermittent expression of genes normally associated with an embryonic state can reverse the hallmarks of old age.

This approach, which not only prompted human skin cells in a dish to look and behave young again, also resulted in the rejuvenation of mice with a premature ageing disease, countering signs of ageing and increasing the animal's lifespan by 30 per cent.

The early-stage work provides insight both into the cellular drivers of ageing and possible therapeutic approaches for improving human health and longevity.

"Our study shows that ageing may not have to proceed in one single direction. It has plasticity and, with careful modulation, ageing might be reversed," said Juan Carlos Izpisua Belmonte, professor at Salk Institute for Biological Studies.

As people in modern societies live longer, their risk of developing age-related diseases goes up.

Data shows that the biggest risk factor for heart disease, cancer and neurodegenerative disorders is simply age.

One clue to halting or reversing ageing lies in the study of cellular reprogramming, a process in which the expression of four genes known as Yamanaka factors allows scientists to convert any cell into induced pluripotent stem cells (iPSCs).

Like embryonic stem calls, iPSCs are capable of dividing indefinitely and becoming any cell type present in our body.

"What we and other stem-cell labs have observed is that when you induce cellular reprogramming, cells look younger.

The next question was whether we could induce this rejuvenation process in a live animal," said Alejandro Ocampo, research associate from Salk Institute.

While cellular rejuvenation certainly sounds desirable, a process that works for laboratory cells is not necessarily a good idea for an entire organism.

For one thing, although rapid cell division is critical in growing embryos, in adults such growth is one of the hallmarks of cancer.

For another, having large numbers of cells revert back to embryonic status in an adult could result in organ failure, ultimately leading to death.

For these reasons, researchers wondered whether they could avoid cancer and improve aging characteristics by inducing the Yamanaka factors for a short period of time.

They turned to a rare genetic disease called progeria.

Both mice and humans with progeria show many signs of aging including DNA damage, organ dysfunction and dramatically shortened lifespan.

Moreover, the chemical marks on DNA responsible for the regulation of genes and protection of our genome, known as epigenetic marks, are prematurely dysregulated in progeria mice and humans.

The study appears in the journal Cell. PTI