Signs of aging safely reversed in mice

 

• Scientists have previously shown that some aspects of cell aging can be reversed in mice.
• However, this was demonstrated in mice with premature aging.
• Other experiments also resulted in the mice developing lethal tumors.
• In the present study, the researchers altered the method by which they reversed the signs of aging in mice, and did so over a longer period of time.
• The researchers found that this method safely reversed various signs of aging in the mice.

The study, published in the journal Nature Aging, lays the ground for research that explores the possibility of translating the findings into humans.

Aging

People have traditionally thought of aging as an inevitable part of life. But since the seminal work of Cynthia Kenyon in the ’90s, researchers have also become aware that aging is under genetic control.

Scientists continue to be interested in finding out whether the negative effects of aging can be reduced or reversed entirely.

Currently, 16% of the United States population is 65 years or older. By 2050 this is expected to reach 22%.

The Centers for Disease Control and Prevention (CDC) noteTrusted Source that aging increases a person’s risk of various serious chronic illnesses, such as cancer, dementia, type 2 diabetes, and heart disease.

The National Institute on AgingTrusted Source points out that there are various things a person can do to help reduce the effects of aging.

These include staying physically active, eating a healthy diet with lots of vegetables, fruit, and whole grains, getting a good amount of quality sleep, avoiding smoking and drinking alcohol, and regularly seeing a doctor.

In 2020 the World Health Organization (WHO) published a baseline report for the Decade of Healthy AgeingTrusted Source, highlighting how countries can go about ensuring health and well-being as people age.

Dr. Tedros Adhanom Ghebreyesus, WHO Director-General, says thatTrusted Source “humans now live longer than at any time in history. But adding more years to life can be a mixed blessing if it is not accompanied by adding more life to years.”

“The Baseline Report for the Decade of Healthy Ageing has the potential to transform the way policy-makers and multiple service providers engage with older adults. We have to work together, to foster the abilities and well-being of our older generations, who continue to give us so much.”

Reprogramming cells

As well as lifestyle and policy changes, scientists are also exploring whether new types of medical interventions could reduce the physiological effects of aging.

The authors behind the present study have previously found that epigenetic markers in mice could be reprogrammed using the molecules Oct4, Sox2, Klf4, and cMyc. These molecules, known as Yamanaka factors, increased the lifespan and reduced the effects of aging in mice with premature aging.

Medical News Today spoke with Prof. Juan Carlos Izpisua Belmonte, of the Gene Expression Laboratory at the Salk Institute for Biological Studies, San Diego, CA, and a corresponding author of the present study.

“In the 2016 paper, we developed a protocol and showed for the first time that Yamanaka factors could be expressed in mice safely without generating cancer. Moreover, in our previous study, we used a premature aging mouse model to demonstrate that Yamanaka factors can extend the lifespan of these mice by preventing the accumulation of aging phenotypes in cells and tissues.”

“However, we did not know if expressing the Yamanaka factors for an extended period of time in animals without any preexisting pathologies will work and whether it would be safe. The goal of the current study was to establish whether long-term partial reprogramming would have a positive or negative impact on a wild-type animal’s health,” said Prof. Izpisua Belmonte.

Mouse models

To do this, Prof. Izpisua Belmonte and his colleagues split the mice into three groups. The first group received Yamanaka factors from 15 to 22 months or around 50 to 70 years in human terms.

The second group received the Yamanaka factors from 12 to 22 months or 35 to 70 in human years.

The third group was treated for a single month at 25 months or 80 years in human terms.

Safe reversal of aging effects

The researchers found that compared with mice that acted as a control, the mice who received the Yamanaka factors did not develop cancer or see any blood cell or neurological changes.

Further, the mice that received the Yamanaka factors for a number of months showed various reversals in the effects of aging.

The kidneys and skin of the mice resembled those of younger mice, their skin healed from wounds without producing as much scarring, and the scientists did not observe the usual metabolic changes in the blood typically seen in older animals.

The animals treated for just a single month late in life did not see these effects.

Prof. Izpisua Belmonte said there were still necessary steps before the research could be tested in humans.

“The translation of our approach to humans requires developing ways to deliver the factors and controlling the levels and how long the factors are expressed. These steps will allow [us] to demonstrate the safe delivery of the factors, a critical aspect before we could start thinking in clinical trials.”

Nonetheless, the findings provide exciting evidence that the technique could have benefits far beyond the reversal of the effects of aging.

“After our initial 2016 study, our lab, as well as several other laboratories around the world, have used the same approach to demonstrate improvement in the regeneration of different tissues in mice and rejuvenation of human cells.”

“All these studies further prove that the controlled expression of Yamanaka factors for cell reprogramming could benefit diverse conditions and might be a general medicine approach in the future for various complications that arise during life,” said Prof. Izpisua Belmonte.

Source: Medical News Today