Ageing process may be reversible, scientists claim

December 17, 2016

Dec 17: Wrinkles, grey hair and niggling aches are normally regarded as an inevitable part of growing older, but now scientists claim that the ageing process may be reversible.

AgeingThe team showed that a new form of gene therapy produced a remarkable rejuvenating effect in mice. After six weeks of treatment, the animals looked younger, had straighter spines and better cardiovascular health, healed quicker when injured, and lived 30% longer.

Juan Carlos Izpisua Belmonte, who led the work at the Salk Institute in La Jolla, California, said: “Our study shows that ageing may not have to proceed in one single direction. With careful modulation, ageing might be reversed.”

The genetic techniques used do not lend themselves to immediate use in humans, and the team predict that clinical applications are a decade away. However, the discovery raises the prospect of a new approach to healthcare in which ageing itself is treated, rather than the various diseases associated with it.

The findings also challenge the notion that ageing is simply the result of physical wear and tear over the years. Instead, they add to a growing body of evidence that ageing is partially – perhaps mostly – driven by an internal genetic clock that actively causes our body to enter a state of decline.

The scientists are not claiming that ageing can be eliminated, but say that in the foreseeable future treatments designed to slow the ticking of this internal clock could increase life expectancy.

“We believe that this approach will not lead to immortality,” said Izpisua Belmonte. “There are probably still limits that we will face in terms of complete reversal of ageing. Our focus is not only extension of lifespan but most importantly health-span.”

Wolf Reik, a professor of epigenetics at the Babraham Institute, Cambridge, who was not involved in the work, described the findings as “pretty amazing” and agreed that the idea of life-extending therapies was plausible. “This is not science fiction,” he said.

The rejuvenating treatment given to the mice was based on a technique that has previously been used to “rewind” adult cells, such as skin cells, back into powerful stem cells, very similar to those seen in embryos. These so-called induced pluripotent stem (iPS) cells have the ability to multiply and turn into any cell type in the body and are already being tested in trials designed to provide “spare parts” for patients.

The latest study is the first to show that the same technique can be used to partially rewind the clock on cells – enough to make them younger, but without the cells losing their specialised function.

“Obviously there is a logic to it,” said Reik. “In iPS cells you reset the ageing clock and go back to zero. Going back to zero, to an embryonic state, is probably not what you want, so you ask: where do you want to go back to?”

The treatment involved intermittently switching on the same four genes that are used to turn skin cells into iPS cells. The mice were genetically engineered in such a way that the four genes could be artificially switched on when the mice were exposed to a chemical in their drinking water.

The scientists tested the treatment in mice with a genetic disorder, called progeria, which is linked to accelerated ageing, DNA damage, organ dysfunction and dramatically shortened lifespan.

After six weeks of treatment, the mice looked visibly younger, skin and muscle tone improved and they lived 30% longer. When the same genes were targeted in cells, DNA damage was reduced and the function of the cellular batteries, called the mitochondria, improved.

“This is the first time that someone has shown that reprogramming in an animal can provide a beneficial effect in terms of health and extend their lifespan,” said Izpisua Belmonte.

Crucially, the mice did not have an increased cancer risk, suggesting that the treatment had successfully rewound cells without turning them all the way back into stem cells, which can proliferate uncontrollably in the body.

The potential for carcinogenic side-effects means that the first people to benefit are likely to be those with serious genetic conditions, such as progeria, where there is more likely to be a medical justification for experimental treatments. “Obviously the tumour risk is lurking in the background,” said Reik.

The approach used in the mice could not be readily applied to humans as it would require embryos to be genetically manipulated, but the Salk team believe the same genes could be targeted with drugs.

“These chemicals could be administrated in creams or injections to rejuvenate skin, muscle or bones,” said Izpisua Belmonte. “We think these chemical approaches might be in human clinical trials in the next ten years.”

The findings are published in the journal Cell.

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News Network
March 6,2020

Mar 6: The spread of the new coronavirus is shining the spotlight on a little-discussed gender split: men wash their hands after using the bathroom less than women, years of research and on-the-ground observations show.

Health officials around the world advise that deliberate, regular handwashing is one of the best weapons against the virus which causes a flu-like respiratory illness that can kill and has spread to around 80 countries.

The Centers for Disease Control and Prevention's online fact sheet "Handwashing: A corporate activity," cites a 2009 study that finds "only 31% of men and 65% of women washed their hands" after using a public restroom.

Social media comments about men's handwashing lapses forced an august British institution to caution visitors about bathroom behaviour this week.

After author Sathnam Sanghera complained on Twitter about "grown," "educated" men in the British Library toilets not washing their hands, the library responded, putting up additional signs reminding patrons to wash their hands in men's and women's bathrooms.

Thanks to "visitor feedback," a spokesman told Reuters, "we have increased further the number of posters in public toilets so that visitors are reminded of the importance of good hygiene at exactly the point where they can wash their hands."

Men and women approach handwashing after using the restroom differently, according to multiple surveys and field studies.

"Women wash their hands significantly more often, use soap more often, and wash their hands somewhat longer than men," according to a 2013 Michigan State University field study conducted by research assistants who observed nearly 4,000 people in restrooms around East Lansing, Michigan.

The study found 14.6% of men did not wash their hands at all after using the bathroom and 35.1% wet their hands but did not use soap, compared to 7.1% and 15.1% of women, respectively.

"If you stand in the men's bathroom at work, and watch men leave, they mostly don't wash their hands if they used the urinal," said one New York City public relations executive, who did not want to be identified for fear of alienating his colleagues.

Since the virus's spread, he's seen an uptick in men's handwashing at work, he noted. "I, for the record, do wash my hands all the time," he added.

Female medical staff in critical care units "washed their hands significantly more often than did their male counterparts after patient contact," a 2001 study published in the American Journal of Infection Control found.

Middle-aged women with some college education had the highest level of knowledge about hand hygiene, a survey published in 2019 by BMC Public Health, an open access public health journal, found.

Early information about coronavirus infection in China shows that men may be more susceptible to the disease. Just over 58% of the more than 1,000 COVID-19 patients reported in China through Jan. 29, 2020, were male, research published in the New England Journal of Medicine shows.

Researchers have not linked the difference to hand hygiene.

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Agencies
May 19,2020

New York, May 19: Cigarette smoke spurs the lungs to make more of the receptor protein which the novel coronavirus uses to enter human cells, according to a study which suggests that quitting smoking might reduce the risk of a severe coronavirus infection.

The findings, published in the journal Developmental Cell, may explain why smokers appear to be particularly vulnerable to severe COVID-19 disease.

"Our results provide a clue as to why smokers who develop COVID-19 tend to have poor clinical outcomes," said study senior author Jason Sheltzer, a cancer geneticist at Cold Spring Harbor Laboratory in the US.

"We found that smoking caused a significant increase in the expression of ACE2, the protein that SARS-CoV-2 uses to enter human cells," Sheltzer said.

According to the scientists, quitting smoking might reduce the risk of a severe coronavirus infection.

They said most individuals infected with the virus suffer only mild illness, if they experience any at all.

However, some require intensive care when the sometimes-fatal virus attacks, the researchers said.

In particular, they said three groups have been significantly more likely than others to develop severe illness -- men, the elderly, and smokers.

Turning to previously published data for possible explanations for these disparities, the scientists assessed if vulnerable groups share some key features related to the human proteins that the coronavirus relies on for infection.

First, they said, they focused on comparing gene activity in the lungs across different ages, between the sexes, and between smokers and nonsmokers.

The scientists said both mice that had been exposed to smoke in a laboratory, and humans who were current smokers had significant upregulation of ACE2.

According to Sheltzer, smokers produced 30-55 per cent more ACE2 than their non-smoking counterparts.

While the researchers found no evidence that age or sex impacts ACE2 levels in the lungs, they said the influence of smoke exposure was surprisingly strong.

However, they said, the change seemed to be temporary.

According to the data, the level of the receptors ACE2 in the lungs of people who had quit smoking was similar to that of non-smokers.

The study noted that the most prolific producers of ACE2 in the airways are mucus-producing cells called goblet cells.

Smoking is known to increase the prevalence of such cells, the scientists said.

"Goblet cells produce mucous to protect the respiratory tract from inhaled irritants. Thus, the increased expression of ACE2 in smokers' lungs could be a byproduct of smoking-induced secretory cell hyperplasia," Sheltzer explained.

However, Sheltzer said other studies on the effects of cigarette smoke have shown mixed results.

"Cigarette smoke contains hundreds of different chemicals. It's possible that certain ingredients like nicotine have a different effect than whole smoke does," he said.

The researchers cautioned that the actual ACE2 protein may be regulated in ways not addressed in the current study.

"One could imagine that having more cells that express ACE2 could make it easier for SARS-CoV-2 to spread in someone's lungs, but there is still a lot more we need to explore," Sheltzer said.

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Agencies
May 14,2020

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

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