[ad_1]
For the 1000 Immunomas project, blood samples were taken from 1,001 healthy individuals aged 8 to 96 years between 2009 and 2016. The samples were subjected to a barrage of analytical procedures determining levels of immune signaling proteins. called cytokines, the state of activation of many immune systems. types of cells in response to various stimuli and the overall activity levels of thousands of genes in each of these cells.
The new study used artificial intelligence to reduce all of that data to a composite that the researchers call an inflammatory clock. The strongest predictors of inflammatory age, they found, were a set of around 50 immune signaling proteins called cytokines. The levels of these, massaged by a complex algorithm, were sufficient to generate a single-digit inflammatory score that well tracked a person’s immunological response and the likelihood of contracting any of the various diseases associated with aging.
In 2017, scientists evaluated nearly 30,000 Immunoma project participants aged 65 or older whose blood was drawn in 2010. They measured the speed of participants getting up from a chair and walking a distance. fixed and, through a questionnaire, their ability to live independently (“Can you walk alone?” “Do you need help getting dressed?”). Inflammatory age was found to be greater than chronological age in predicting frailty seven years later.
Next, Furman and his colleagues obtained blood samples from an ongoing study of exceptionally longevity people in Bologna, Italy, and compared the inflammatory ages of 29 of these people (all but a centenarian) with those from 18 years old from 50 to 79 years old. -old. The elderly had inflammatory ages on average 40 years below their civil age. One of them, a 105-year-old man, had an inflammatory age of 25, Furman said.
To further assess the effect of inflammatory age on mortality, Furman’s team turned to the Framingham study, which has tracked the health outcomes of thousands of people since 1948. The Framingham study was lacking in Sufficient data on hematogenous protein levels, but the genes whose activity levels largely dictate the production of inflammatory clock cytokines is well known. The researchers measured the activity levels of these genes encoding cytokines in the cells of Framingham’s subjects. This proxy for cytokine levels was significantly correlated with all-cause mortality among Framingham participants.
A key substance
Scientists observed that blood levels of a substance, CXCL9, contributed more powerfully than any other component of the clock to the inflammatory age score. They found that levels of CXCL9, a cytokine secreted by certain immune cells to attract other immune cells to a site of infection, begin to rise rapidly after the age of 60, on average.
Among a new cohort of 97 people aged 25 to 90 selected in the 1000 Immunomas project for their apparently excellent health, with no signs of disease, the researchers looked for subtle signs of cardiovascular deterioration. Using a sensitive arterial stiffness test, which shows an increased risk of stroke, heart attack and kidney failure, they linked high inflammatory age scores – and high levels of CXCL9 – unexpected arterial stiffness and another sign of unfortunate cardiac consequences: the excessive thickness of the wall of the main pumping station of the heart, the left ventricle.
CXCL9 has been implicated in cardiovascular disease. A series of experiments in laboratory dishes showed that CXCL9 is secreted not only by immune cells, but also by endothelial cells, the main components of the walls of blood vessels. Researchers have shown that advanced age both correlates with a significant increase in endothelial cell CXCL9 levels and decreases the ability of endothelial cells to form microvascular networks, expand and contract.
But in laboratory experiments carried out on mouse tissues and human cells, the reduction in CXCL9 levels restored juvenile endothelial cell function, suggesting that CXCL9 directly contributes to the dysfunction of these cells and that its inhibition may occur. proven effective in reducing the risk of cardiovascular disease in susceptible individuals. .
“The ability of our inflammatory aging clock to detect accelerated subclinical cardiovascular aging foreshadows its potential clinical impact,” said Furman. “All disorders are best treated when they are treated early. “
The other co-authors of the Stanford study are Robert Tibshirani, PhD, professor of biomedical data science and statistics; Trevor Hastie, PhD, professor of statistics and biomedical data; principal investigator Lu Cui, PhD; Director of Immunoassays, Center for Human Immunity Surveillance Yael Rosenberg-Hasson, PhD; former instructor in neurology Benoit Lehalier, PhD; former postdoctoral researcher Shai Shen-Orr, PhD; Holden Maecker, PhD, professor of microbiology and immunology; Cornelia Dekker, MD, professor of pediatric infectious diseases, emeritus; Tony Wyss-Coray, PhD, professor of neurology and neurological sciences; François Haddad, MD, clinical professor of cardiovascular medicine; Jose Montoya, MD, former professor of infectious diseases; Joseph Wu, MD, professor of radiology and director of the Stanford Cardiovascular Institute; and Mark Davis, PhD, professor of microbiology and immunology and director of the Institute for Immunity, Transplantation and Infection.
Researchers from Buck Institute, Edifice Health, University of North Carolina, Technion-Israel Institute of Technology, University of Louvain, University of Bologna, University of Florence and the Institute of Neurological Sciences in Bologna also contributed to the work.
The work was funded by Stanford Alzheimer’s Disease Research Center, Buck Institute for Research on Aging, Ellison Foundation, National Institutes of Health (grants U19 AI057229, U19 AI090019, UL1 RR025744, K01 HL135455 and P50 AG047366) and the Paul F Glenn Foundation.
[ad_2]
Source link