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Researchers unlock secrets of ageing in blood stem cells

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Researchers studied the production of blood cells from the bone marrow, in 10 individuals ranging from new-born to elderly

New research has uncovered how genetic changes that accumulate slowly in blood stem cells throughout life are likely to be responsible for the dramatic change in blood production after the age of 70.

The study, by scientists at the Wellcome Sanger Institute, the Wellcome-MRC Cambridge Stem Cell Institute and collaborators, was published on June 1 in the journal Nature, and suggests a new theory of ageing.

“We’ve shown, for the first time, how steadily accumulating mutations throughout life lead to a catastrophic and inevitable change in blood cell populations after the age of 70,” said Dr Peter Campbell, senior researcher from the Wellcome Sanger Institute, and senior researcher on the study.

“What is super exciting about this model is that it may well apply in other organ systems too.

“We see these selfish clones with driver mutations expanding with age in many other tissues of the body – we know this can increase cancer risk, but it could also be contributing to other functional changes associated with ageing.”

Somatic mutations

All human cells acquire genetic changes throughout life, known as somatic mutations.

Ageing is likely to be caused by the accumulation of multiple types of damage to our cells over time, with one theory being that build-up of somatic mutations causes cells to progressively lose functional reserve.

However, it is currently unclear how such gradual accumulation of molecular damage could translate into the abrupt deterioration in how our organs function after the age of 70 years.

To investigate this ageing process, the team from the Wellcome Sanger Institute, the Cambridge Stem Cell Institute and collaborators studied the production of blood cells from the bone marrow, analysing 10 individuals ranging in age from new-borns to the elderly.

They sequenced the whole genomes of 3,579 blood stem cells, identifying all the somatic mutations contained in each cell.

Family trees

The team used this to reconstruct ‘family trees’ of each person’s blood stem cells, showing, for the first time, an unbiased view of the relationships among blood cells and how these relationships change across the human lifespan.

The researchers found that these ‘family trees’ changed dramatically after the age of 70 years.

The production of blood cells in adults aged under 65 came from 20,000 to 200,000 stem cells, each of which contributed in roughly equal amounts.

In contrast, blood production in individuals aged over 70 was very unequal.

A reduced set of expanded stem cell clones – as few as 10 to 20 – contributed as much as half of all blood production in every elderly individual studied.

These highly active stem cells had progressively expanded in numbers across that person’s life, caused by a rare subset of somatic mutations known as ‘driver mutations’.

These findings led the team to propose a model in which age-associated changes in blood production come from somatic mutations causing ‘selfish’ stem cells to dominate the bone marrow in the elderly.

Reduced diversity

This model, with the steady introduction of driver mutations that cause the growth of functionally altered clones over decades, explains the dramatic and inevitable shift to reduced diversity of blood cell populations after the age of 70.

Which clones become dominant varies from person to person, and so the model also explains the variation seen in disease risk and other characteristics in older adults.

A second study, also published June 1 in Nature, explores how different individual driver mutations affect cell growth rates over time.

“Our findings show that the diversity of blood stem cells is lost in older age due to positive selection of faster growing clones with driver mutations,” said Dr Emily Mitchell, lead researcher from Addenbrooke’s Hospital and the Sanger Institute.

“These clones ‘outcompete’ the slower growing ones.

“In many cases this increased fitness at the stem cell level likely comes at a cost – their ability to produce functional mature blood cells is impaired, so explaining the observed age-related loss of function in the blood system.”

Dr Elisa Laurenti,joint senior researcher from the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge, also spoke on the research.

“Factors such as chronic inflammation, smoking, infection and chemotherapy cause earlier growth of clones with cancer-driving mutations,” she said.

“We predict that these factors also bring forward the decline in blood stem cell diversity associated with ageing.

“It is possible that there are factors that might slow this process down, too.

“We now have the exciting task of figuring out how these newly discovered mutations affect blood function in the elderly, so we can learn how to minimise disease risk and promote healthy ageing.”

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Space station partnership for bioprinting research

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Starlab Space has announced a partnership with Auxilium Biotechnologies to advance 3D bioprinting in orbit.

Auxilium will provide orbital 3D bioprinting and biofabrication capabilities (manufacturing biological materials) aboard the Starlab space station to support research and development in regenerative medicine, implantable medical devices and tissue engineering.

Regenerative medicine uses the body’s own materials to repair damage or replace diseased tissue.

Auxilium’s proprietary AMP-1 3D bioprinter has demonstrated the mass production of implantable medical devices and other complex structures, such as perfusable blood vessels, in microgravity, the very low gravity environment in space, aboard the International Space Station.

In November 2024, Auxilium created tiny, functional blood vessels aboard the International Space Station using its AMP-1 platform.

These vessels, with wall thicknesses about the width of a human hair, were produced in under an hour, which is not possible on Earth, where the process requires more time, materials and complex steps.

With Starlab, Auxilium aims to accelerate translation from experimental biology to manufacturable products, positioning AMP-1 as what it describes as a production facility for the next generation of life science technologies in space.

“3D printing in microgravity enables tissue architectures and material properties not achievable under standard 1g manufacturing,” said Isac Lazarovits, director of engineering at Auxilium.

“This biomanufacturing facility on board the future Starlab space station will expand access to low Earth orbit, lower barriers for industry and academia, and enable high-impact research and manufacturing that will benefit Earth.”

Microgravity enables enhanced protein crystallisation for drug development, 3D cell growth and disease modelling that aims to better replicate human biology, and stem cell research with potential applications for treating conditions such as Parkinson’s disease, diabetes and Alzheimer’s. Stem cells are cells that can develop into different cell types.

“This partnership demonstrates Starlab’s commitment to fostering innovation in life sciences,” said Marshall Smith, chief executive of Starlab.

“By providing companies like Auxilium with the infrastructure to advance biomanufacturing in microgravity, we’re creating pathways for breakthrough therapies that will improve lives on Earth.”

Starlab’s design enables full certification and operation within weeks, according to the company, which says this minimises delays and maximises efficiency for payload customers.

Through joint venture partners, customers can conduct research on the International Space Station, with the aim of ensuring a seamless transition to Starlab for future work.

Starlab Space is a US-led global joint venture among Voyager Technologies, Airbus, Mitsubishi Corporation, MDA Space, Palantir Technologies and Space Applications Services, with strategic partners including Hilton, Journey, Northrop Grumman and The Ohio State University.

Auxilium Biotechnologies develops bioprinting and biomanufacturing solutions and implantable medical devices.

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Two teas or coffees a day could lower dementia risk, experts say

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People who drink two to three cups of coffee or tea daily have a lower dementia risk, new research suggests.

Health records for more than 130,000 people showed that over 40 years, those who routinely drank two to three cups of caffeinated coffee or one to two cups of caffeinated tea daily had a 15 to 20 per cent lower risk compared with those who went without.

The caffeinated coffee drinkers also reported slightly less cognitive decline, a measure of how thinking and memory deteriorate over time, than those who opted for decaf and performed better on some objective tests of brain function.

The findings suggest habitual tea and coffee drinking may be good for the brain, but the research cannot prove it, as caffeine drinkers may be less prone to dementia for other reasons.

The study was led by Yu Zhang, who studies nutritional epidemiology at Harvard University.

A similar link would arise if poor sleepers, who appear to have a greater risk of cognitive decline, steered clear of caffeine to get a better night’s rest.

“Our study alone can’t prove causality, but to our knowledge, it is the best evidence to date looking at coffee and tea intake and cognitive health, and it is consistent with plausible biology,” Zhang said.

Coffee and tea contain caffeine and polyphenols, plant compounds that may protect against brain ageing by improving vascular health and reducing inflammation and oxidative stress, where harmful atoms and molecules called free radicals damage cells and tissues.

Substances in the drinks could also work by improving metabolic health. Caffeine, for example, is linked to lower rates of type 2 diabetes, a known risk factor for dementia.

The researchers analysed records of 131,821 volunteers enrolled in two big US public health studies, the Nurses’ Health Study and the Health Professionals Follow-up Study.

Both took repeated assessments of the participants’ diets, dementia diagnoses, any cognitive decline they experienced and scores on objective cognitive tests for up to 43 years.

Overall, men and women who drank the most caffeinated coffee had an 18 per cent lower risk compared with those who had little or none, with similar results seen for tea.

The effect seemed to plateau at two to three cups of caffeinated coffee or one to two cups of caffeinated tea. No link was found between decaffeinated coffee and dementia.

Further work is needed to confirm whether the two drinks actually protect the brain.

Gold standard trials that randomly assign people to drink caffeinated or decaffeinated drinks for decades before checking for differences in dementia diagnoses are largely impractical.

However, studies could explore whether the drinks drive biological changes linked to brain function, which could be spotted in scans or other tests, Zhang said.

Naveed Sattar, a professor of cardiometabolic medicine at the University of Glasgow, said getting clarity would not be easy, not least because caffeine can have good and bad effects on the brain.

Tea and coffee both contain antioxidants that may be beneficial, and a caffeine boost can motivate people to work, learn and exercise.

In some people, caffeine raises blood pressure, a significant driver of dementia.

“Caffeine does a multitude of things, some which may be beneficial, some which may be harmful, and the net effect can never be estimated until you do a randomised trial,” Sattar said.

Researchers believe about half of dementia cases worldwide can be prevented or delayed by tackling factors such as obesity, smoking, excessive alcohol consumption, hearing loss and high blood pressure.

“Don’t think of coffee or tea as a magic shield,” Zhang said.

“I’d say maintaining a healthy lifestyle, getting regular exercise, having a balanced diet and getting good sleep are all important to get better brain health.”

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Genetic influence on lifespan underestimated by half

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People are twice as likely to inherit their lifespan as previously thought, new research suggests.

The genetic contribution to how long a person lives is around 50 per cent, based on health databases in Denmark and Sweden. This reflects heritability, the share of lifespan differences due to genes.

For decades, many scientists believed genes and ancestry accounted for between about 10 and 25 per cent of longevity.

The research was led by scientists at the Weizmann Institute in Israel, with the Karolinska Institute in Sweden and Leiden University.

The earlier underestimates arose from limited historic health and mortality data, where deaths due to war, infectious disease, risky or unsafe work, accidents, poor diet and lack of medical care were hard to separate in records.

“For many years, human lifespan was thought to be shaped almost entirely by non-genetic factors, which led to considerable scepticism about the role of genetics in ageing and about the feasibility of identifying genetic determinants of longevity,” said Ben Shenhar of the Weizmann Institute.

Environmental forces such as disease or living conditions can mask or confound potential genetic effects.

Hereditary causes of death, for those not killed first by external causes, mean “processes originating within the body, including genetic mutations, age-related diseases and the decline of physiological function with age.” the researchers said.

“If heritability is high, as we have shown, this creates an incentive to search for gene variants that extend lifespan, in order to understand the biology of ageing and, potentially, to address it therapeutically.” said Shenhar.

Other recent research has pointed to a potential role for taurine, an amino acid, in slowing the ageing process.

Scientists have also highlighted the bowhead whale’s 200-year lifespan, attributed to a cellular protein that may protect against carcinogenic mutations.

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