Science

Scientists develop an inflammatory ageing CLOCK to predict frailty

An inflammatory ageing clock can predict how strong your immune system is and when you’ll become frail by analysing your blood, according to its developers.

The AI-driven device can diagnose life-threatening illness years before any symptoms begin to develop, allow for early treatment and improved recovery.

The system can also determine frailty levels in old age seven years in advance, say researchers from the Buck Institute for Research on Aging in Novato, California

The US team analysed blood samples from 1,001 individuals aged eight to 96 years as part of a project called ‘1000 Immunomes’, to create a prediction score.

It’s even more accurate than the number of candles on your birthday cake, say scientists from Stanford University School of Medicine, who also worked on its development, as it is based on blood-borne proteins that drive chronic inflammation.

The study authors say the system detects your iAge, or immune age, based on proteins in your blood that are linked to ageing and frailty. 

Detecting a chronic or life-threatening illness early allows time for any lifestyle changes or medication to take hold, before any permanent damage is done.

An inflammatory ageing clock can predict how strong your immune system is and when you’ll become frail by analysing your blood, according to its developers. Stock image

CHEMOKINE CXCL9 LINKED TO AGE-RELATED FRAILTY 

Chemokine (C-X-C motif) ligand 9 (CXCL9), a small cytokine that plays a role in the immune system. 

Stanford University researchers explored the role of cytokines in ageing by using AI to examine the blood of people at different points in their lives.

They found that levels of cytokines are significantly linked to mortality rates from all diseases. 

One cytokine, known as CXCL9, contributed more than any other to a factor known as the iAge.

This is the immune age, the differing rates at which people’s immune systems decline, becoming less effective as we grow older and leading to inflammation. 

The cytokine is secreted by certain immune cells to attract others to a site of an infection and soars after people reach the age of 60.

It was found to be strongly associated with hardening of the arteries, heart attacks and strokes and is also found in endothelial cells that line the walls of blood-vessels.

Old age correlated with a significant increase in CXCL9 – diminishing the ability to form micro-vascular networks that dilate and contract.

In lab experiments on human cells and tissue from mice, reducing levels of CXCL9 restored youthful endothelial-cell function.

It suggests CXCL9 directly contributes to dysfunction – and inhibiting it combats cardiovascular disease.

This helped the Stanford team develop a system to predict frailty in advance. 

Senior author Professor David Furman, from the Buck Institute, said the calendar might tell us we are a year old, but not all humans age biologically at the same rate.

‘You see this in the clinic – some older people are extremely disease-prone, while others are the picture of health,’ he explained.

The phenomenon is due to differing rates at which people’s immune systems decline, becoming less effective as we grow older and leading to inflammation.

As they become less effective, it fuels organ damage and life threatening conditions – including cardiovascular disease, cancer and dementia.

Now a metric has been developed that measures the process for the first time by the Buck Institute and Stanford researchers, built on the idea levels of immune cells and proteins fluctuate throughout life – known as a persons’s ‘iAgee’. 

Professor Furman said the clock opens the door to curing illnesses – or at the very least staving them off through early intervention.

The US team analysed blood samples from 1,001 individuals aged eight to 96 years as part of a project called ‘1000 Immunomes’.

Those with an older iAge showed patterns of systemic inflammation sooner, the team discovered, adding they were also prone to multiple long-term health problems including lowered immunity, cardiovascular disease and frailty. 

The strongest predictors were a set of around 50 proteins called cytokines, that enabled the artificial intelligence ‘brain’ to generate an inflammatory score. 

It tracked a person’s immunological response – and the likelihood of incurring any of a variety of ageing-related diseases.

When the researchers assessed the fitness of about 30 over 65s seven years later, ‘iAge’ proved superior to chronological age in predicting frailty.

They measured the participants’ speed at getting up from a chair, walking a fixed distance and their ability to live independently.

Dr Furman and colleagues also obtained blood samples from 29 exceptionally long-lived people in Italy and found their iAge was 40 years younger than their real age. 

One, a 105-year-old man, had an inflammatory age of 25, said Furman.

Results were confirmed through data from the Framingham Study, which has tracked the health of people from the Massachusetts town since 1948.

Levels of cytokines were significantly linked to mortality rates from all diseases and one cytokine, known as CXCL9, contributed more than any other to iAge. 

The cytokine is secreted by certain immune cells to attract others to a site of an infection and soars after people reach the age of 60.

It was found to be strongly associated with hardening of the arteries, heart attacks and strokes and is also found in endothelial cells that line the walls of blood-vessels.

The AI-driven device can diagnose life-threatening illness years before any symptoms begin to develop, allow for early treatment and improved recovery. Stock image

The AI-driven device can diagnose life-threatening illness years before any symptoms begin to develop, allow for early treatment and improved recovery. Stock image

Ageing process has NOT slowed down in humans due to biological constraints 

From vitamins to health plans, exercise programs and strict dieting regimes, the available options for lengthening our lifespan are in abundance.

But a new scientific study from biologists suggests they’re all totally useless, as there’s nothing humans can do to ‘cheat death’. 

The study authors, representing 42 institutions across 14 countries, analysed information on humans and 30 non-human primates. 

They found that all species have succeeded in living longer over time by reducing the rates of infant and juvenile mortality, due to better living conditions. 

Since 1850, the average human life expectancy has gone from a meagre 40-ish years to 70-something. 

And the fact that human life expectancies have improved over the last couple of hundred years may suggest we’re gradually warding off ageing as a species.  

But unfortunately, researchers found this is not the case – it’s just because more individuals are living much longer due to a fall in deaths at younger ages. 

The increase, they say, is more likely the statistical outcome of improved survival for children and young adults, not slowing the ageing clock. 

Old age correlated with a significant increase in CXCL9 – diminishing the ability to form micro-vascular networks that dilate and contract.

In lab experiments on human cells and tissue from mice, reducing levels restored youthful endothelial-cell function.

It suggests CXCL9 directly contributes to dysfunction – and inhibiting it combats cardiovascular disease, according to Furman.

‘Our inflammatory ageing clock’s ability to detect sub-clinical accelerated cardiovascular ageing hints at its potential clinical impact. All disorders are treated best when they’re treated early,’ he explained.

Adding: ‘Standard immune metrics which can be used to identify individuals most at risk for developing single or even multiple chronic diseases of aging have been sorely lacking.

‘Bringing biology to our completely unbiased approach allowed us to identify a number of metrics, including a small immune protein which is involved in age-related systemic chronic inflammation and cardiac ageing.

‘We now have means of detecting dysfunction and a pathway to intervention before full-blown pathology occurs.’

When it comes to health and longevity, the age of a person’s immune system trumps the chronological information from a driver’s license. 

‘On average, centenarians have an immune age that is 40 years younger than what is considered ‘normal’ and we have one outlier, a super-healthy 105 year-old man – who lives in Italy – who has the immune system of a 25 year old,’ said Furman.

He says iAge can be used to track someone’s risk of developing multiple chronic diseases by assessing the cumulative physiological damage to their immune system. 

‘Using iAge it’s possible to predict seven years in advance who is going to become frail. That leaves us lots of room for interventions,’ he explained.

The system can also determine frailty levels in old age seven years before it happens, say researchers from the Buck Institute for Research on Aging in Novato, California. Stock image

The system can also determine frailty levels in old age seven years before it happens, say researchers from the Buck Institute for Research on Aging in Novato, California. Stock image

In 2013 a group of researchers studying ageing identified nine ‘hallmarks’ of the ageing process. Age-related immune system dysfunction was not part of the mix.

Prof Furman said: ‘It’s becoming clear we have to pay more attention to the immune system with age, given that almost every age-related malady has inflammation as part of its etiology.

‘If you’re chronically inflamed, you will have genomic instability as well as mitochondrial dysfunction and issues with protein stability.

‘Systemic chronic inflammation triggers telomere attrition, as well as epigenetic alterations.

‘It’s clear that all of these nine hallmarks are, by and large, triggered by having systemic chronic inflammation in your body. I think of inflammation as the 10th hallmark.’

The clock is described in Nature Aging.

HOW MIGHT SCIENTISTS USE TELOMERASE TO REVERSE THE PROCESS OF AGEING?

Scientists decoded an enzyme thought to halt ageing in plants, animals and humans as part of a recent breakthrough study.

Unravelling the structure of the complex enzyme, called telomerase, could lead to drugs that slow or block the ageing process, along with new treatments for cancer, researchers reported in the journal Nature in April.

Elated scientists announced the completion of a 20-year quest to map the enzyme thought to forestall ageing by repairing the tips of chromosomes.

‘It has been a long time coming,’ lead investigator Kathleen Collins, a molecular biologist at the University of California in Berkeley, said in a statement.

‘Our findings provide a structural framework for understanding human telomerase disease mutations, and represent an important step towards telomerase-related clinical therapeutics.’

Part protein and part RNA (genetic material that relays instructions for building proteins) telomerase acts on microscopic sheaths, known as telomeres, that cover the tips of the chromosomes found inside all cells.

In humans, each cell contains 23 pairs of chromosomes, including one pair of sex chromosomes – the ‘X’ and ‘Y’ – that differ between males and females.

Australian-American biologist Elizabeth Blackburn, who shared the 2009 Nobel Prize in Medicine for discovering telomeres and their protective function in the 1970s, likened them to the tiny plastic caps that keep shoelaces from fraying.

Eventually, however, shoelace tips and telomeres do break down: every time a cell divides the telomeres get worn a little bit more, until the cell stops dividing and dies. This, biologists agree, is probably central to the natural ageing process.


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