Aug 15th 2018

Ageing in human cells successfully reversed in the lab

by Lorna Harries and Matt Whiteman

 

Lorna Harries is Associate Professor in Molecular Genetics, University of Exeter

Matt Whiteman is Professor of Experimental Therapeutics, University of Exeter

 

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.

A senescent cell. Eva Latorre, Author provided

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 know that 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.

Lorna Harries, Associate Professor in Molecular Genetics, University of Exeter and Matt Whiteman, Professor of Experimental Therapeutics, University of Exeter

This article was originally published on The Conversation. Read the original article.

Browse articles by author

More Essays

Nov 19th 2021
EXTRACTS: "At a time when the struggle between authoritarianism and democracy is so intense, if not fateful for the future of democracies, NATO and the EU must warn these countries [Editor's note: Poland and Hungary, EU and NATO, Turkey NATO] that they are on the precipice of being kicked out if they do not change their governing practice. They must be required to restore the principles of democracy by upholding universal human rights and abiding the rule of law, or else they will forfeit their membership and suffer from the consequences of their crimes." ------ "A narcissistic leader, such as Trump, whose hunger for power seems to know no limit, has happily sacrificed the good of the country on the altar of his twisted ego. America’s democracy cannot be repaired unless he and those who helped him are held accountable and face the weight of the law."
Nov 18th 2021
EXTRACT: "Many people who go through intense trauma, for example, become deeper and stronger than they were before. They may even undergo a sudden and radical transformation that makes life more meaningful and fulfilling. Indeed, research shows that between half and one-third of all people experience significant personal development after traumatic events, such as bereavement, serious illness, accidents or divorce. Over time, they may feel a new sense of inner strength and confidence and gratitude for life and other people. They may develop more intimate and authentic relationships and have a wider perspective, with a clear sense of what is important in life and what isn’t. In psychology, this is referred to as “post-traumatic growth”. "
Nov 11th 2021
EXTRACT: "Notably, Murdoch thinks that really knowing or understanding another person is a difficult task: “It is a task to come to see the world as it is”. According to the Freudian psychology Murdoch subscribes to in The Sovereignty of Good, humans are prone to “fantasy” – refusing to face the truth because it can damage our fragile egos."
Nov 9th 2021
EXTRACT: "People do not believe false information because they are ignorant. There are many factors at work, but most researchers would agree that the belief in misinformation has little to do with the amount of knowledge a person possesses. Misinformation is a prime example of motivated reasoning. People tend to arrive at the conclusions they want to reach as long as they can construct seemingly reasonable justifications for these outcomes."
Oct 28th 2021
EXTRACTS: "Brood with me on the latest delay of the full release of the records pertaining to the murder of President John F. Kennedy in Dallas on November 22, 1963. That was 58 years ago." -----"Mark my words: ...... No one who remembers 1963 will live to see the US government admit the full truth about Kennedy’s murder. And the American people’s faith in democracy will continue to fade. There is only one way to prevent this, and that is to release every record, withholding nothing – and to do it now."
Oct 27th 2021
EXTRACT: "..... we may defy the warnings of modern medicine, convinced of our own superiority. Researchers at the University of Chicago Divinity School reported half of their participants, all of whom indicated some religious affiliation, agreed with the statement “God will protect me from being infected”. To cope with our dread of death, we delude ourselves into thinking we are invincible: death might happen to other people, but not to me."
Oct 22nd 2021
EXTRACT: "Wes Anderson’s new film The French Dispatch is about the final issue of a magazine that specialises in long-form articles about the goings-on in the fictional town of Ennui-sur-Blasé. The film is an anthology of shorts representing three of the articles. A piece by the magazine’s art critic (Tilda Swinton) explores the life and late success of the abstract artist Moses Rosenthaler (Benicio Del Toro). Talented from a young age, Rosenthaler pursued art with a dogged determination that drove him to slowly lose his mind." ---- "Like everything else, mental illness is understood within the context of its time. In their study of melancholy and genius Born Under Saturn, the art historians Margot and Rudolf Wittkower show how Renaissance artists embraced mental alienation. This was shown by a withdrawn, slothful gloom. Such heavy sadness was considered both the symptom and the price of divine inspiration." ---- "Today, the association of creativity and mental illness often implies regression from an adult and orderly state of mind to one that is primal, impulsive, or infantile. The artist in Anderson’s film is such an example: he is noisy, impetuous, and extravagantly mad. And it is while he is at his “maddest” that he paints his best work." ---- "Here I explore the work of four painters whose work has been shaped by various mental illnesses, highlighting how the idea of the “mad artist” need not be tied up with a loss of control but rather a bid to gain it."
Oct 21st 2021
EXTRACT: "So much of Succession holds a mirror to real life, and the way that Logan Roy’s hand-picked board members allowed these abuses to continue by turning a blind eye to them is a good example. We have just published research that shows that public companies whose directors are chosen by their CEOs are statistically more likely to be involved in corporate misconduct, along with various other shortcomings. So why does this happen, and what should be done about it? "
Oct 10th 2021
EXTRACT: "Born in Zanzibar in 1948, Gurnah came to Britain in the 1960s as a refugee. Being of Arab origin, he was forced to flee his birthplace during the revolution of 1964 and only returned in 1984 in time to visit his dying father. Until his retirement, he was a full-time professor of English and postcolonial literatures at the University of Kent in Canterbury."
Oct 7th 2021
EXTRACT: "As the 25th James Bond film No Time to Die hits the cinemas, we are once again reminded of the way that disability is depicted negatively in Hollywood films. The new James Bond film features three villains, all of who have facial disfigurements (Blofeld, Safin and Primo). If you take a closer look at James Bond villains throughout history, the majority have facial disfigurements or physical impairments. This is in sharp contrast to the other characters, including James Bond, who are able-bodied and presented with no physical bodily differences. Indeed, many films still rely on outdated disability tropes, including Star Wars and various Disney classics. Rather than simply being part of a character’s identity, the physical difference is exploited and exaggerated to become a plot point and visual metaphor for villains" ----- "The British Film Institute (BFI) was the first organisation to sign up and has committed to stop funding films that feature negative representations depicted through scars or facial differences – a step in the right direction."
Oct 5th 2021
EXTRACT: "The trillions of microbes inside of our gut play many very important roles in our body. Not only does this “microbiome” regulate our metabolism and help us absorb nutrients from food into the body, it can also influence whether we are lean or obese."
Sep 16th 2021
EXTRACTS: "Hyperbaric oxygen therapy involves breathing pure oxygen in a pressurised chamber. In the chamber, the air pressure is increased two to three times higher than normal air pressure. It is commonly used to treat decompression sickness (a condition scuba divers can suffer from), carbon monoxide poisoning,......" ---- "Blood flow to the brain is reduced in people with Alzheimer’s. This study showed increased blood flow to the brain in the mice receiving oxygen therapy, which helps with the clearance of plaques from the brain, and reduces inflammation – a hallmark of Alzheimer’s." ----- "The researchers then used these findings to assess the effectiveness of oxygen therapy in six people over the age of 65 with cognitive decline. They found that 60 sessions of oxygen therapy, over 90 days, increased blood flow in certain areas of the brain and significantly improved the patients’ cognitive abilities – improved memory, attention and information processing speed."
Sep 14th 2021
EXTRACT: "Hollywood for years called on Charles Boyer to typify one French look –  bedroom eyes, sly maneuverings, the dismissive look. A face of another type, the massive mug and narrow eyes of Charles de Gaulle, provides the same disdain of the foreigner but also a superiority based on his belief in his own destiny."
Sep 12th 2021
EXTRACT: "The burden of loneliness for older people is intimately connected to what they are alone with. As we reach the end of our lives, we frequently carry heavy burdens that have accumulated along the way, such as feelings of regret, betrayal and rejection. And the wounds from past relationships can haunt people all their lives."
Sep 5th 2021
EXTRACT: "Gardens help restore the ability to concentrate on demanding tasks, providing the perfect space for a break when working from home in a pandemic. Natural things – such as trees, plants and water – are particularly easy on the eye and demand little mental effort to look at. Simply sitting in a garden is therefore relaxing and beneficial to mental wellbeing."
Aug 17th 2021
EXTRACT: "Whether or not a person achieves remission, reducing blood sugar levels is important in managing the negative effects of type 2 diabetes and reducing risk of complications. But when it comes to choosing a diet, the most important thing is to pick one that suits you – one that you’re likely to stick to long term."
Aug 10th 2021
EXTRACT: "In our latest study, we show that by taking the microbiome from young mice and transplanting them into old mice, many of the effects of ageing on learning and memory and immune impairments can be reversed. Using a maze, we showed that this faecal microbiota transplant from young to old mice led to the old mice finding a hidden platform faster."
Aug 3rd 2021
EXTRACT: "Fukuyama argued that political struggle causes history. This struggle tries to solve the problem of thymos – an ancient Greek term referring to our desire to have our worth recognised. This desire can involve wanting to be recognised as equal to others. But it can also involve wanting to be recognised as superior to others. A stable political system needs to accommodate both desires." .... "Counter-dominant spite can weaken liberal democracies. During the 2016 Brexit referendum, some people in the UK voted Leave to spite elites, knowing this could damage the country’s economy. Similarly, during the 2016 US presidential election some voters supported Donald Trump to spite Hillary Clinton, knowing his election could harm the US. "
Jul 31st 2021
EXTRACT: "If we want to live in a world that is good for pollinators, as well as the rest of us, big changes are needed in our environment, and our food system. This is why many beekeepers change their diet and their shopping, eating more locally grown vegetables that aren’t treated with pesticides. ...... Being willing to buy fruit and vegetables that may have the occasional insect living in it is better for us and for nature. To live more harmoniously with the natural world, we need to relax about larvae in the lettuce and slugs in the spinach."
Jul 22nd 2021
EXTRACT: "You’d think our brush with mortality through the pandemic would have brought some of this home to us. You’d think it would give us pause for thought about what really matters to us: the kind of world we want for our children; the kind of society we want to live in. And for many people it has. In a survey carried out during lockdown in the UK, 85% of respondents found something in their changed conditions they felt worth keeping and fewer than 10% wanted a complete return to normal."