University of Arizona Regents Professor of Psychology, Neurology and Neuroscience and Director of the University of Arizona Evelyn F. McKnight Brain Institute

Dr. Carol Barnes was recently awarded a $60 million grant from the National Institutes of Health to create and lead a Precision Aging Network that could transform the way we think about the aging brain. In this blog post, Dr. Barnes shares her insights on the keys to aging successfully, as well as what exciting new research is on the horizon to help us better understand why people experience brain aging differently.

Q: Based on your experience studying humans and animals to better understand brain aging and memory, what do you see as the key differentiators between people who age successfully and are only slightly affected by normal brain aging and those who experience dementia and other diseases of learning and memory?

A: I can best answer that question by focusing on what we still do not understand. We still don’t understand why some people have a slow, steady decline in cognition, while some decline faster and some succumb to dementia. Understanding what controls that trajectory is at the heart of my research program and what we’ll be exploring with the Precision Aging Network grant I was recently awarded. It’s important that we start by understanding how to optimize cognition as we age because you can’t understand dementias without first understanding the normal biological processes that are going on with aging. The illnesses that lead to dementia are superimposed on top of the normative aging brain. 

One approach to understanding why some people are so resilient is to study those people – people who are super agers with superior longevity. Motivated by the observation that particular genes are good markers of if people are resilient or susceptible to disease, one gene that’s been found to be very critical to memory is NPX2. Research has found that people with Alzheimer’s and plaques and tangles in the brain show reduced levels of NPX2 and some people with plaques and tangles in the brain, but with high levels of NPX2 are not cognitively impaired and are asymptomatic of Alzheimer’s disease. We’re uncovering this as a really interesting marker to predict what your trajectory is going to be. Presumably if you could manipulate NPX2 as a marker, we could optimize cognition in people. It’s a very exciting avenue to pursue. If we can determine how to manipulate this marker, it could be a breakthrough in determining why some people are more resilient than others. 

Q2: Some exciting studies in animal models suggest that transfusing older animals with blood from younger animals makes them resilient to cognitive decline. What are your thoughts on such studies? Are they likely to lead to treatments to prevent age-related cognitive decline in humans?

A: With blood transfusion treatment, we don’t know the mechanisms of why it works, but we do know that it works. In research I conducted at a satellite lab at UC Davis, we worked with geriatric and young monkeys and were excited to propose a non-human primate model test to determine the mechanisms of why what has been shown in mice and rats works. Unfortunately, the company sponsoring the work decided not to invest in the study and we were unable to continue going forward with the blood transfusions. 

There is a paper published in December 2021 about the integrated stress response that has promising findings. The integrated stress response mechanism is elevated in aging and an inhibitor has been developed to reverse the response. The data looks very strong and shows that after three days of injections to reverse the integrated stress response process throws a switch in the brain that changes the response to one of a younger person – with a young immune profile – and the effects may last for months. This needs to be investigated further, but is also a very exciting development in the field.

Q3: From the MindCrowd study to the Reserve and Resilience Consortium, you are involved with many exciting studies and initiatives. How would you say the MindCrowd approach of recruiting the general public and allowing anyone interested to participate will help achieve the study’s end goal of helping people keep their cognitive abilities as they age? 

A: With the MindCrowd study, we are working to understand aspects of cognition broadly – by examining a wider group of people than just those who come to the university to participate in studies. We’re trying to get data from and look at large groups of people. With the MindCrowd online test, we now have data from more than 250,000 people collected – making it the largest online study.

We’ve evolved the project into the Precision Aging Network Grant and are now collecting metrics from people who take the MindCrowd test online and following up to get additional data crossing all states and reaching across all racial and ethnic groups and socio-economic levels. We’re trying to get half a million participants that we’ll cluster in groups to identify interventions for people with things like cardiovascular issues or depression and figure out how to change their trajectory by finding the best interventions to close the gap between your cognitive health span and longevity. Our goal is to study a wide reaching group of people and determine how to optimize cognitive health for as long as people live.