Predicting Which Organs Will Fail First

"We can estimate the biological age of an organ in an apparently healthy person," said the study's senior author, Tony Wyss-Coray, PhD, a professor of neurology and the D. H. Chen Professor II. "That, in turn, predicts a person's risk for disease related to that organ."

"Numerous studies have come up with single numbers representing individuals' biological age -- the age implied by a sophisticated array of biomarkers -- as opposed to their chronical age, the actual numbers of years that have passed since their birth," said Wyss-Coray, who is also the director of the Phil and Penny Knight Initiative for Brain Resilience.

This study identified distinct numbers for each of the 11 key organs, organ systems or tissues: heart, fat, lung, immune system, kidney, liver, muscle, pancreas, brain, vasculature, and intestine. Wyss-Coray said that while only 1 in 60 participants had two organs undergoing accelerated aging, they had 6.5 times the mortality rate of a person without any pronouncedly aging organs. 

"When we compared each of these organs' biological age for each individual with its counterparts among a large group of people without obvious severe diseases, we found that 18.4% of those age 50 or older had at least one organ aging significantly more rapidly than the average," Wyss-Coray said. "And we found that these individuals are at heightened risk for disease in that particular organ in the next 15 years."

The study started with checking levels of nearly 5,000 proteins in blood samples from close to 1,400 healthy people between the ages of 20-90 years old and flagging all proteins whose genes were 4 times more highly activated in one organ compared to any other organ. Close to 900 organ-specific proteins were found, which was reduced to 858 for reliability reasons. 

A deep learning machine algorithm was trained to guess ages based on the levels of the proteins, training it to pick proteins that best correlate with a trait of interest such as accelerated biological aging in a person or a particular organ, and if the protein enhances the correlation. The algorithm accuracy was verified by assessing the ages of close to another 4000 people who somewhat represent the American general population. 

Next, the proteins were used to zero in on each of the 11 selected organs, measuring levels of organ-specific proteins within each participant’s blood. The research found that there was modest aging in synchrony among the separate organs, but the individual organs largely had their own path along the aging process. 

An age gap was found for each of the 11 organs, and the identified age gaps for 10 out of the 11 the only exception was the intestine) organs studied were significantly associated with future risk of death from all causes over a 15-year follow-up. 

Having an accelerated aging organ was found to have a 15% to 50% higher risk of mortality over the next 15 years, depending on which organ was affected. Those with accelerated heart aging were at 2.5 times as high a risk of heart failure compared to those with normally aging hearts. Those with aging brains were 1.8 times more likely to display cognitive decline over 5 years compared to their counterparts. There were also strong associations between extreme-aging (more than 2 standard deviations) kidney scores and both hypertension and diabetes, as well as between an extreme-aging heart score and both atrial fibrillation and heart attack. 

"If we can reproduce this finding in 50,000 or 100,000 individuals," Wyss-Coray said, "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."