The Visible Layer of Parkinson’s: What We See Is Only the Surface

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The visible layer is only the surface

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The second episode in the Parkinson’s series by Liat Portal, written with Dr. Minna Schmidt, examines the visible layer of Parkinson’s and the hidden biology underneath it. It connects family observation, aging research, the Buck Institute for Research on Aging, and the question of what science can study before symptoms become fully visible.

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In Parkinson’s, visibility is not just emotional. It is scientific, cultural, and structural. What becomes visible can change diagnosis, funding, patient participation, research direction, and the way families understand what they are seeing.

In this installment, I’m connecting the dots between my uncle, Henry Portal, Michael J. Fox, Ozzy Osbourne, Dr. Minna Schmidt’s research at The Buck Institute for Research on Aging, and the long road toward earlier detection and better treatments.

Even before my conversation with Minna, I knew I didn’t know enough about Parkinson’s, except for what people can notice with their eyes, even if they are not doctors, such as shaking, trembling, stiffness, and the body not moving as expected.

Unfortunately, I gained some experience knowing that the most common symptoms are not the only signs of a disease when my grandfather developed Alzheimer’s. Before he was diagnosed, all we knew was that Alzheimer’s damages the brain and causes memory loss, but it was only after 3 years of changes in his behavior that we found out that it was much more than just memory loss. The symptoms were all there; however, we didn’t know how to read them.

Therefore, my immediate assumption was that I didn’t know enough, which Minna, a researcher studying Parkinson’s disease (PD), confirmed, since Parkinson’s symptoms go beyond just involuntary trembling of limbs or inability to control body parts.

That was the point where I understood that what I knew was only the visible layer. I knew the symptoms people can see from the outside, but I did not understand the body systems, the aging process, or the research questions behind them. Minna’s part begins there, with the scientific explanation of why Parkinson’s may start long before the disease becomes clear to families, patients, and doctors.

Minna:

Parkinson’s is commonly recognized by its most visible symptoms, such as tremor, slowed movement, and loss of physical control. However, research now suggests the disease may begin years, sometimes decades, before those symptoms appear, progressing through different body systems, including the gut microbiome, the vagus nerve, and the brain. Aging is implicated, and ongoing studies at The Buck Institute for Research on Aging aim to answer questions through this lens. What we see is the surface. The process of Parkinson’s starts much earlier underneath.

I work at The Buck Institute for Research on Aging, founded in 1999 and the world’s only institute dedicated solely to the study of aging. At The Buck, each lab focuses on a particular disease (e.g., cancer, neurodegeneration, or diabetes) or on the process of aging. The University of Southern California (USC), where I received my PhD jointly with The Buck Institute for Research on Aging, houses the country’s first school offering PhD, master’s, and bachelor’s degrees in Gerontology. Importantly, many of its former faculty, including my Principal Investigator (PI), Dr. Julie Andersen, were among The Buck’s first hires. In Dr. Andersen’s lab, we focus on Parkinson’s disease and Alzheimer’s disease (AD).

Why Study Aging?

Aging is a complex process that sometimes requires long periods of study. It is thought to be the root cause of many diseases, such as Parkinson’s and Alzheimer’s. Fundamental discoveries in this field have shown that it is possible to modify the process of aging through dietary, exercise, chemical, or genetic interventions. However, living longer doesn’t necessarily mean living healthier. This is why many researchers today focus not only on extending human lifespan but also on human healthspan — the number of years lived without serious disease.

Image 1. The twelve hallmarks of aging

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Today, it seems normal to study a disease like Parkinson’s in the context of aging, but this hasn’t always been the case. Aging continues to be perceived as a background process. It is often cited as the reason for many ailments and is sometimes used as an excuse to say, ‘it is what it is.’ This is not an attitude we take at The Buck — aging means something very concrete to the scientists who work here. But while aging seems to drive many problems, is it possible to study it on its own when it is so ingrained in our biology?

Some incredible discoveries have helped answer this exact question! Not only did these experiments show that aging depends on specific genes and processes in various model organisms*, but they also demonstrated that it is possible to extend lifespan, sometimes by as much as 10 times, with various genetic, chemical, drug, dietary, and exercise interventions. Many of The Buck’s first scientists played important roles in these early discoveries (including my co-PI, Dr. Gordon Lithgow), and together with all former and current faculty, The Buck has been highly successful in demonstrating that aging is a unique process and that it can be methodically altered.

*Animals that serve as models of a disease or condition and are treated according to a strict, ethically approved experimental protocol.

It’s Not So Easy!

However, studying a disease in the context of age is not easy. Studies are often conducted in a model organism, which requires the organism to live out its full lifespan. For some organisms, such as the roundworm Caenorhabditis elegans (C. elegans), this can mean waiting just shy of a full month, whereas for others, like the mouse, it can mean that experimental results will be available in 2–3 years (!). Furthermore, experiments, naturally, don’t always go as planned — for example, the intervention you sought may not produce the expected result. While this is still very important information (a negative result), it took a considerable amount of time to learn that your hypothesis was incorrect!

…But Perhaps We Can Find the Right Approach!

While these difficulties, compounded by a still-developing understanding of aging (today, scientists have 12 hallmarks of aging (Image 1), including inflammation, dysbiosis, and genetic alterations), may preclude scientists from studying disease and aging together, it is important to pursue this path in the context of age-related diseases such as Parkinson’s. To address these challenges, scientists have assembled the International Network for Parkinson’s Disease Modeling and AGEing (PD-AGE), consisting of scientists from the aging and Parkinson’s fields, including Dr. Julie Andersen, funded by The Michael J. Fox Foundation. Its goal is to provide methodological approaches that can systematically address questions about age and Parkinson’s in model organisms.

I was very lucky to participate in the PD-AGE brainstorming sessions as an Early Career Researcher (ECR), and the sub-group I worked with recently published a roadmap for Parkinson’s aging studies in mice. Two other sub-groups published on induced pluripotent stem cells (iPSCs) and non-human primates. Ultimately, these experimental approaches will seek to uncover novel therapeutic interventions for Parkinson’s, informed by knowledge and interventions from studies in the aging field.

This was the second episode in the Parkinson’s series by Liat Portal, written with Dr. Minna Schmidt. It explains the difference between what people see from the outside and what science is trying to understand underneath the visible symptoms.

Read the complete series:

1. The Portal Into Parkinson’s: The Symptoms My Family Did Not Know How to Read
2. The Visible Layer of Parkinson’s: What We See Is Only the Surface
3. Back to the Future of Parkinson’s: Michael J. Fox, Ozzy Osbourne, and the Shock of Seeing It Young
4. Forward to the Past: Michael J. Fox and the Disease That Was Moving Before the World Could See It
5. When Visibility Becomes Infrastructure: Michael J. Fox, Fox Insight, and the Data That Changed Parkinson’s Research
6. Into the Void: Ozzy Osbourne, Sharon Osbourne, and the Parkinson’s Timeline Nobody Read Correctly
7. Paranoid, Fragile, and Still on Stage: Ozzy Osbourne, Sharon, and the Visibility Parkinson’s Needed
8. The Buck Institute, the Microbiome, and the Data Parkinson’s Research Still Needs

***The Liat Show is a multi-domain story universe unfolding across domains in real time, powered by readers. To receive new posts, join as a free or paid subscriber on Substack and stay ahead of the next chapter before the door closes. Annual and founding members enter the story before the rest of the world understands it.***

🧠 Q&A

What is this story about? This story is about the visible layer of Parkinson’s and the science underneath it. It asks why symptoms that families can see may appear only after hidden biological processes have already been active.

Why does the story mention Alzheimer’s? The Alzheimer’s comparison shows how symptoms can exist before families understand what they are seeing. It creates a human bridge into the scientific problem of recognizing disease earlier.

What does aging research add to Parkinson’s? Aging research treats aging as a biological process rather than only a background condition. This matters because Parkinson’s and Alzheimer’s are age-related diseases, and understanding aging may help researchers identify better approaches to treatment and prevention.

What is the role of The Buck Institute for Research on Aging in this episode? The Buck Institute for Research on Aging provides the scientific setting for Minna’s work. The episode explains why an institute focused on aging is relevant to Parkinson’s research and why model organisms are used to study questions that unfold over time.

What is the central idea of this episode? The central idea is that what we see is only the surface. Parkinson’s may begin long before the visible symptoms appear, and research is trying to understand what happens underneath.

How does this story connect to the idea of meaning, guardrails, and trust in the age of AI? This story shows why meaning must be preserved alongside information. A visible symptom can be misunderstood without context, and scientific information can lose value if it is detached from the human experience that gives it urgency. Guardrails in AI should protect context, source, and interpretation so knowledge remains accurate, connected, and trustworthy.

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***The Liat Show is a multi-domain story universe unfolding across domains in real time, powered by readers. To receive new posts, join as a free or paid subscriber on Substack and stay ahead of the next chapter before the door closes. Annual and founding members enter the story before the rest of the world understands it.***