"Body and mind do not age separately. They are in constant conversation"

Aging is shaped by a continuous interplay between body and mind. Mara Mather explains how physiological and emotional changes influence healthy aging and outlines the questions driving her future research.
 

You're joining the Institute as a new director. What will you add to the Institute's research landscape?

I bring about 20 years of research on emotion, memory, and aging. For a long time, my focus was on how emotional experiences shape what we remember. But the deeper I went into those questions, the clearer it became that the body is not a passive bystander to the brain. The autonomic nervous system—the system that controls your heart, your organs, your inner state of calm—plays a central role. That connection between the autonomic and the affective is what interests me most right now. That's why my new center is called the Center for Affective and Autonomic Neuroscience (CAAN).

What is the central scientific problem you want to solve?

The overarching goal is to understand how changes in the autonomic nervous system—changes that begin in early adulthood—set the stage for neurodegenerative disease, specifically, Alzheimer's disease. The pathological processes do not begin in old age. They begin decades earlier, in some people even in childhood. Biomarkers in the tau and amyloid pathways of the disease—the two interacting instigators of the disease—already show clear changes when people are in their twenties. What nobody has really investigated is why.

Is that why you're taking a closer look at the early phase of the disease?

Exactly. Post-mortem data show that all of the brains examined over 30 years of age already have tau-related pathological changes in the locus coeruleus. This small region in the brainstem is the primary source of the brain's noradrenaline. By the seventh decade, nearly all cases show Alzheimer's pathology in the cortex in addition to in the locus coeruleus. This isn't something that affects only some of us. It affects all of us, to varying degrees and at varying speeds.

What do we know about the biological processes driving these early changes?

Imagine two protein processes unfolding in parallel. Amyloid beta is a normal byproduct of neuronal activity, constantly produced and—especially during sleep—cleared out of the brain. In young adulthood, the amount of this peptide in the cerebrospinal fluid rises dramatically; once it reaches a certain level, it starts to aggregate into plaques. Meanwhile, the tau protein already begins to form pre-tangle structures in the locus coeruleus in people's twenties and thirties, then spreads over decades into the memory regions of the brain. Both processes move very slowly and both are influenced by what is happening in the body. That is exactly where the autonomic nervous system enters the picture.

In what way?

A healthy heart doesn't beat like a metronome. It speeds up slightly when you inhale and slows down when you exhale. This subtle responsiveness is called heart rate variability, and it reflects how active your parasympathetic nervous system is: the branch of the autonomic nervous system responsible for rest and recovery. The more variability, the better your body is at shifting into a calm, restorative state.

What we see is that this variability drops sharply as we age, and the decline starts surprisingly early. Data from eight million fitness tracker users show an 80% decline between 20 and 60 years of age, with the steepest drop happening in the early twenties. At the same time, the opposing system, the sympathetic or "fight-or-flight" branch, becomes increasingly dominant, driving up noradrenaline levels and blood pressure.

This shift matters beyond cardiovascular health. Noradrenaline doesn't just raise your heart rate; it also stimulates the biochemical pathways that produce amyloid beta. Normally, the parasympathetic system acts as a brake on this process. But when that brake weakens with age, production can accelerate, which may be one reason amyloid starts to accumulate in the brain long before any symptoms of Alzheimer's appear.

Another major focus of your work is the role of emotion in aging. How does that connect?

This is perhaps the most fascinating paradox. Older adults often show an autonomic profile that, in a younger person, would be interpreted as a sign of psychological disorder: reduced heart rate variability, increased sympathetic activation, and elevated blood pressure. Low heart rate variability, in particular, is a transdiagnostic marker of psychopathology, appearing consistently across conditions such as depression, anxiety, and bipolar disorder. Yet despite this physiological profile, older adults typically report higher levels of emotional well-being, show a tendency to remember more positive than negative information, and demonstrate superior emotion regulation. This pattern is known as the positivity effect.

How do you explain that contradiction?

My hypothesis is that the brain notices the body is out of balance and tries to compensate. The prefrontal cortex is constantly monitoring the body state. When it receives signals of an overactive sympathetic system, it pushes back, with a side effect on attention: the brain begins to preferentially notice positive, calming content. Not fully successfully, as the heart rate variability stays low. But it changes how the brain perceives the world. The aging brain puts on a pair of rose-colored glasses. Not out of naivety, but out of necessity. And this brings me back to the central insight: Body and mind do not age separately. They are in constant conversation, adjusting and compensating. Understanding that conversation is exactly what my new Center is for.

What makes the Institute the right place for this research?

At this Institute, there is both the infrastructure and the intellectual freedom to ask fundamental questions and let the research evolve organically. This is particularly important for my work, which involves developing and refining methods rather than simply applying established ones.

Studying a region like the locus coeruleus is technically demanding—it is a very small structure, deep in the brainstem, and simply not visible with standard imaging. High-resolution magnetic resonance imaging (MRI) changes that. Access to that technology here is not a nice-to-have; it is what makes certain questions answerable at all. And alongside that technical capacity, the collaborative atmosphere—the opportunity to develop ideas across disciplines—is equally important.

Are there collaborations you are especially excited about?

Very much so. There are strong connections to environmental research, for example, examining how natural environments support parasympathetic activity, while factors like air pollution may contribute to early brain pathology especially in the locus coeruleus. I'm also interested in how emotional aging shapes interactions with emerging technologies, including Artificial Intelligence. And there are exciting overlaps with decision science, particularly in understanding how emotion and attention influence risk assessment and choices across the lifespan. Finally, affective and autonomic states are important modulators of synaptic change and so are key to understanding the mechanisms of brain plasticity.

Do you already have concrete projects in mind for the first years?

The first major study, in close collaboration with the Charité, will test whether slow‑paced breathing can reduce amyloid‑beta levels in the brain itself. Our clinical trials at the University of Southern California showed reductions in plasma amyloid‑beta levels after four to five weeks of daily slow breathing. Plasma can reflect many processes, so the next step is measuring cerebrospinal fluid (CSF) before and after the intervention in a randomized controlled trial. If we see the same effect we observed in plasma, that will indicate that slow breathing is also influencing amyloid beta levels in the brain, with direct implications for how the field thinks about Alzheimer's prevention.

Alongside that, we will begin the longitudinal study of autonomic function in people aged 20 to 40 years. This is the age range that has been almost entirely overlooked and where, we believe, the most important early changes are taking place.

On a personal level, what are you most looking forward to in this new chapter?

What I love about science is that I'm always learning and that I get to be part of an exciting detective story. My favorite scientific problems involve data that contradict our current theories or assumptions. It's here that we can really learn new things by trying to figure out how to explain these surprising patterns. I'm particularly motivated to shed light on the relationships between autonomic/noradrenergic activity and the early precursors to Alzheimer's disease. Elucidating these links could inform population-level interventions to slow disease progression, with potentially far-reaching societal impact. To be in an environment with the tools, the colleagues, and the institutional support to pursue those questions properly, over years and with the depth they deserve, is truly exciting.