Scientists Have Managed To Reverse The Ageing Of Human-Cells In A Lab

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The new research could be the first step to new anti-degenerative drugs.

The ability to reverse ageing is something many people would hope to see in their lifetime. This is still a long way from reality, but in our latest experiment, we have reversed the ageing of human cells, which could provide the basis for future anti-de­generation drugs.

Ageing can be viewed as the pro­gressive decline in bodily function and is linked with most of the com­mon chronic diseases that humans suffer from, such as cancer, diabetes and dementia. There are many rea­sons why our cells and tissues stop functioning, but a new focus in the biology of ageing is the accumula­tion of “senescent” cells in the tis­sues and organs.

Senescent cells are older dete­riorated cells that do not function as they should, but also compromise the function of cells around them. Re­moval of these old dysfunctional cells has been shown to improve many fea­tures of ageing in animals such as the delayed onset of cataracts.

We still don’t fully understand why cells become senescent as we age, but damage to DNA, exposure to inflammation and damage to the protective molecules at the end of the chromosomes – the telomeres – have all been suggested.

More recently, people have sug­gested that one driver of senescence may be loss of our ability to turn genes on and off at the right time and in the right place.

One gene, many messages

As we age, we lose our ability to control how our genes are regulated. Each cell in the body contains all the information needed for life, but not all genes are switched on in all tis­sues or under all conditions. This is one of the ways that a heart cell is dif­ferent from a kidney cell, despite the fact they contain the same genes.

When a gene is activated by sig­nals from inside or outside the cell, it makes a molecular message (called an RNA) that contains all the infor­mation needed to make whatever that gene makes. We now knowthat over 95% of our genes can actually make several different types of messages, depending on the needs of the cell.

A good way to think about this is to consider each gene as a recipe. You could make either a vanilla sponge, or a chocolate cake, depending on whether you include the chocolate. Our genes can work like this. The de­cision as to which type of message is produced at any given time is made by a group of about 300 proteins called “splicing factors”.

As we age, the amount of splicing factors we are able to make declines. This means that aged cells are less able to switch genes on and off to respond to changes in their environ­ment. We and others have shown that the levels of these important regula­tors decline in blood samples from elderly humans, and also in isolated human senescent cells of different tis­sue types.

Rejuvenating old cells

We have been looking for ways to turn the splicing factors back on. In our new work, we showed that by treating old cells with a chemical that releases small amounts of hydrogen sulphide, we were able to increase levels of some splicing factors, and to rejuvenate old human cells.

Hydrogen sulphide is a molecule that is found naturally in our bodies and has been shown to improve sev­eral features of age-related disease in animals. But it can be toxic in large amounts, so we needed to find a way to deliver it directly to the part of the cell where it is needed.

By using a “molecular postcode” we have been able to deliver the mol­ecule directly to the mitochondria, the structures that produce energy in cells, where we think it acts, allowing us to use tiny doses, which are less likely to cause side effects.

We are hopeful that in using mo­lecular tools such as this, we will be able to eventually remove senescent cells in living people, which may allow us to target multiple age-related dis­eases at once. This is some way in the future yet, but it’s an exciting start.

By arrangements with The Conversation.

  

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