US scientists reverse signs of ageing in mice

Washington, Dec 16 (IANS) US researchers have successfully reversed the hallmarks of ageing in mice using a technique called cellular reprogramming.

The approach extended the lifespan of mice with a premature aging disease called progeria by 30 per cent, Xinhua news agency cited a US journal Cell report as saying.

"Our study shows that aging may not have to proceed in one single direction," Juan Carlos Izpisua Belmonte, a professor at the Salk Institute's Gene Expression Laboratory and senior author of the study, said.

"It has plasticity and, with careful modulation, aging might be reversed," said Izpisua Belmonte.

Cellular reprogramming is a process that involves inducing the expression of four genes, Yamanaka factors, to allow scientists to convert any cell into induced pluripotent stem cells, which are capable of dividing indefinitely and becoming any cell type present in our body.

For cells to reach pluripotency, the expression of Yamanaka factors typically takes two to three weeks.

However, previous efforts involving cellular reprogramming resulted in mice that either died immediately or developed extensive tumours.

In the new study, the Salk team used a partial cellular reprogramming approach, which induced expression of Yamanaka factors for just two to four days, to avoid tumours or death and improve aging characteristics.

When they examined skin cells from mice with progeria using this approach, the cells showed reversal of multiple aging hallmarks without losing their skin-cell identity.

Encouraged by this result, the team used the same method to treat live mice with progeria, which delivered "striking" results.

Compared to untreated mice, the reprogrammed mice looked younger; their cardiovascular and other organs improved and most surprising of all, their lifespan went from 18 weeks to 24.

"This study shows that aging is a very dynamic and plastic process, and therefore will be more amenable to therapeutic interventions than what we previously thought."

The researchers explained their partial reprogramming approach works by alerting the genome's chemical marks, known as epigenetic marks, which change over a lifetime in response to environmental changes, regulate and protect the genome.

"This work shows that epigenetic changes are at least partially driving aging," said first author Paloma Martinez-Redondo, a Salk research associate.

"It gives us exciting insights into which pathways could be targeted to delay cellular aging."

The researchers believed that induction of epigenetic changes via chemicals or small molecules may be the most promising approach to achieve rejuvenation in humans.

However, they cautioned that due to the complexity of aging these therapies may take up to 10 years to reach clinical trials.