番茄社区

About one in five healthy people ages 50 and older had an organ that was aging at an accelerated rate, which may increase mortality and signal organ-specific disease, a study of nearly 5,700 people suggested.

In an analysis of blood samples for proteins originating from specific organs, 18.4% of people 50 and older had one organ with accelerated aging and 1.7% had aging in multiple organs, reported Tony Wyss-Coray, PhD, of Stanford University in California, and co-authors.

When the biological age of an organ was much greater than the chronological age of the person, there was a 20% to 50% higher risk of mortality and organ-specific diseases, they noted in .

For instance, people with accelerated heart aging had a 250% increased risk of heart failure, while accelerated brain and vascular aging predicted Alzheimer's disease progression as accurately as plasma phosphorylated tau 181 (p-tau181), a high-performing Alzheimer's biomarker. Accelerated aging in kidneys was associated with diabetes, obesity, hypercholesterolaemia, and hypertension, and accelerated aging in muscles was linked with gait impairment.

Notably, heart attack and Alzheimer's disease, among other diseases, were associated with accelerated aging in "virtually all organs," while others were only associated with aging of one organ or a subset of organs.

Particularly significant at the population level were aged kidneys. Hypertensive individuals had kidneys that were, on average, a year older than their same-age peers, while people with diabetes had kidneys that were about 1.3 years older. People with atrial fibrillation had hearts 2.8 years older, and those who had a heart attack had hearts that were 2.6 years older.

"If we can reproduce this finding in 50,000 or 100,000 individuals, it will mean that by monitoring the health of individual organs in apparently healthy people, we might be able to find organs that are undergoing accelerated aging in people's bodies, and we might be able to treat people before they get sick," Wyss-Coray said in a .

The researchers measured 4,979 proteins from participants' blood samples. They then mapped the putative organ-specific plasma proteome and used that to train machine learning models to guess people's age based on those protein levels. Eleven key organs, organ systems, or tissues were assessed: heart, fat, lung, immune system, kidney, liver, muscle, pancreas, brain, vasculature, and intestine.

After finding that 15% of the proteins could be attributed to a specific organ, "we basically had now a list of proteins that, in a way, gave us organ-specific information in the blood and then we used this for each organ to make a biological clock," Wyss-Coray told 番茄社区, adding that "we don't age in synchrony across our whole body."

The study included data from the Covance, LonGenity, Stanford Alzheimer's Disease Research Center, Stanford Aging Memory Study, and Knight Alzheimer's Disease Research Center cohorts. The researchers used SomaLogic SomaScan to quantify proteins in plasma and the Gene Tissue Expression Atlas human tissue bulk RNA-seq database to identify which genes and plasma proteins were organ-enriched, defined as being expressed at least four times higher in a particular organ; the highest number was in the brain.

Using machine learning, they estimated biological age using the plasma proteome and then calculated the organ age gap. The researchers also developed the feature importance for biological aging (FIBA) algorithm, "which uses feature permutation to generate a per-protein importance score for both chronological and biological age," to investigate how proteins contributed to brain aging.

Because the study focused on a subset of organs, it is unknown if these findings apply to all organs. Wyss-Coray and team also noted that they observed "many instances of nonlinear dynamics in the plasma proteome and in aging phenotypes," urging caution in extrapolating the results to people younger than 50. They also suggested that the research be conducted among more ethnically and geographically diverse populations, since the participants were majority white and entirely American.

Wyss-Coray added that he hopes future studies will assess multiple blood samples from patients across time to see how organ aging changes. "We may gain new insight into the biological mechanisms that lead to that heart aging," he said.

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