New test could identify your body's ‘weakest link' as you age, Stanford research finds
Additionally, the scientists found that older-appearing organs are associated with a higher risk of developing a disease or other complication in that organ. Of most interest, though, was the brain: An 'extremely aged' brain was associated not only with an increased risk of developing Alzheimer's disease, but a 182% increased risk of dying in the next 15 years.
The work was based on an assessment of nearly 45,000 participants who contributed to a European biobank that collects blood samples and other health information. It was published Wednesday in the journal Nature Medicine.
'This test opens the possibility for a relatively simple assessment of the state of your body — of the different organs — and identifying the weakest link as you get older,' said Tony Wyss-Coray, senior author of the study and director of the Knight Initiative for Brain Resilience at Stanford. 'It's almost like a sentinel that we can listen to and it tells us if there is something going on with this organ that isn't normal.'
The Stanford work adds to a growing catalog of research into aging and how scientists can best monitor it and, ultimately, slow it down. There are now a variety of tools, including body scans, that can help scientists understand the aging process in individual organs. Taken all together, these tools could someday be used in the doctor's office to help patients make health care decisions.
'There are more of these things emerging to track aging, especially in the brain,' said Saul Villeda, associate director of the Bakar Aging Research Institute at UCSF. Villeda was not involved in the Stanford work, but he said it looked promising and he could imagine it being one of several strategies for monitoring people's health.
'Maybe we could use multiple approaches,' Villeda said. 'You can imagine an elderly person gets a brain scan and their blood taken, and from that we can understand if a therapy is working.'
The Stanford test looks at the levels of organ-specific proteins in the blood. Wyss-Coray's team studied nearly 3,000 proteins in each participants' blood; about 15% of the proteins could be traced to a single organ, meaning only the heart or lung or some other organ produced that protein.
The scientists first used samples from about 20,000 individuals to train an artificial intelligence model that determined the expected protein levels for a given organ at a certain chronological age. Then, scientists determined the difference between individuals' actual protein levels and the expected levels based on their age.
A difference of more than 1.5 standard deviation from the average organ placed someone in the 'extremely aged' or 'extremely youthful' category. A third of people in the study had at least one organ that was extremely old or extremely young; one fourth of people had multiple old or young organs.
The scientists next looked at health outcomes for the individuals in the study. Generally, an older organ was associated with a greater risk of disease in that organ. But the association was especially powerful for the brain and the risk of dementia.
People with extremely old brains had a three-times greater risk of developing Alzheimer's disease than those with normal brains; their risk was 12 times greater compared to people with extremely young brains. In fact, having an extremely old brain carried the same risk of Alzheimer's as having the APEO4 gene, the primary genetic risk factor for the disease.
That association wasn't surprising, Wyss-Coray said, but the associated risk of death from having an older brain was unexpected. Not only were extremely old brains tied with a significantly increased risk of dying, but extremely young brains were associated with a 40% reduction.
People with older brains 'had the highest risk of mortality of all the other organs that we looked at,' Wyss-Coray said, though he couldn't explain why there was such a strong association. 'Maybe it's the central role of the brain in orchestrating our body and regulating all body function, ultimately.'
There remain many questions about the test results and how they could be applied, Wyss-Coray said. The test could be commercially available in two or three years, but how much it will cost and how people will access it is not yet clear. Wyss-Coray said the test costs about $1,000 for research purposes.
He noted that the test has ethical considerations — not everyone will want to know the age of their internal organs, especially if they feel like there's not much they can do to change their status.
But Wyss-Coray's team also looked at the role of lifestyle behaviors on protein levels, and found that things like exercise and not smoking were tied to younger organs. Unlike genetic testing, which may reveal risks people can do very little about, an organ protein test could help people narrow down where they want to focus their lifestyle improvements, Wyss-Coray said.
But he added that more research is needed to determine whether lifestyle changes would have a direct impact on organ age. For example, he'd now like to conduct double-blinded trials looking at whether certain lifestyle interventions are reflected in an organ's age.
'I have tested myself with an early version,' Wyss-Coray said, 'but I'm going to test myself again. I want to know. I think I can do something about it.'
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These images show that treatment of the Alzheimer mice with a very low dose of lithium orotate almost completely abolishes both the plaques and the tangle-like structures. Yankner Lab Other scientists not involved in the research said the findings create a new approach to designing medications to treat and prevent Alzheimer's. 'This study is looking at it from a novel angle,' said 'I didn't expect that the lithium level [in our body] would be this critical,' she said. 'I just hadn't thought about it this way.' The amount of lithium in medications used for mental health conditions is very high and can be toxic to elderly patients. But the amount of lithium used by Yankner's team was one-thousandth the level, essentially mimicking the amount naturally found in the brain. Indeed, mice fed tiny amounts throughout their adult life showed no signs of toxicity. Earlier research has suggested a link between sustained intake of lithium and lower levels of dementia. Notably, Advertisement 'When we're thinking about the therapeutics of a replacement, if you're lowering something, you just have to replace it back to the natural levels,' he said. 'That seems a lot safer than introducing something that our body is not used to, or doesn't already need in order to function. ' 'That's a really good rationale for pursuing it,' he said. A number of factors are linked through research to a higher risk of Alzheimer's and dementia including advanced age, family history, and genetics, as well as several modifiable factors such as diet, smoking, hypertension and diabetes. Liviu Aron, first author of the study that links lithium deficiency to Alzheimer's disease, looked at samples of human and mouse brains in the Harvard lab on Aug. 4. Heather Diehl/For The Boston Globe Many foods already touted for their health benefits naturally contain higher amounts of lithium — But Kaeberlein and other researchers said the real test of the Harvard team's findings would be a large clinical trial in people, with half of the participants receiving small doses of lithium orotate and the others a sham substance, to compare the findings. Kaeberlein said the safety track record of this form of lithium, which showed no toxicity in animals, may help speed trials in people. Advertisement The Harvard findings 'line up with a lot of earlier work, both in the brain and in normal aging,' Kaeberlein said. And he added something rarely heard from scientists when discussing cutting-edge research and a potential medication that may fundamentally change the course of a dreaded disease. This work, he said, 'feeds my optimism that this will lead to potential therapeutics.' But one obstacle to advancing the research is the freeze on Kay Lazar can be reached at
