How Proteomics Is Rewriting Our Understanding of Aging: An Interview With Dr. Birgit Schilling

As interest in aging biology rises among scientists and the general public, few researchers sit as squarely at the crossroads of technology, translational research, and human health as Dr. Birgit Schilling. Schilling is a professor at the Buck Institute for Research on Aging and director of its mass spectrometry core facility. 

Her research focuses on identifying the molecular changes that accompany aging and age-related disease, using high-resolution proteomics methods.

During the Human Proteome Organization (HUPO) 2025 conference, Schilling sat down with Technology Networks to discuss how cellular senescence affects brain aging, how proteomics helps unite different scientific disciplines, and what future technologies might enable.

Mapping senescence across the aging brain

Schilling is part of the National Institutes of Health Cellular Senescence Network (SenNet), which gives her access to rare human tissues, including healthy aging spinal cord samples that are difficult to obtain for molecular research.

Using mass spectrometry (MS), her team searches for “senescence signatures”. These are proteins that rise or fall with age and may signal early dysfunction. Many of these overlap with pathways associated with Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease.

“There’s a real progression between healthy aging and diseases like Alzheimer’s or ALS, and understanding that shift is key to intervening,” she said. “Senescence is one of the most basic mechanisms of aging... we see it in the brain, the kidney, the lung, everywhere.”

Schilling explains that these signatures are not identical across tissues. Every organ appears to have its own “portfolio” of senescent proteins, a pattern that may help to explain why aging manifests so differently from person to person.

Collaborative steps towards interventions

The Buck Institute is known for its focus on age-related diseases, and Schilling collaborates closely with neuroscientist Dr. Lisa Ellerby to translate proteomic findings into biological insights. Together, they are exploring whether clearing senescent cells could slow or prevent neurodegeneration.

“These are the first experiments where we have treated Alzheimer’s mouse models with senolytics—it is still early, but it’s a real step toward intervention,” Schilling said.

They utilize a combination of systems: mouse models, human induced pluripotent stem cell-derived cerebral organoids, and preserved human brain and spinal cord tissue from clinical programs. “Each brings strengths and pitfalls, but together they keep us grounded in human biology,” she noted.

Investigating the bone–brain axis

One of the most surprising findings presented in her HUPO talk emerged from a collaboration with skeletal biologist Dr. Tamara Alliston and Ellerby.²* Although epidemiological studies have identified a link between osteoporosis, fractures, and cognitive decline, the intricate science behind the bone–brain connection has remained unclear.

In a mouse model of Alzheimer’s disease, Schilling’s team assessed both the hippocampus and the femur bone.

“The most amazing thing we found was that in the female bones of these Alzheimer’s mouse models, the bone became brittle—even though these are brain disease models,” she said. At the proteomic level, the bone showed extensive remodeling.

The discovery raises questions about signaling between the bone and brain. If a therapy improves neural health, could it also benefit skeletal integrity? Could improving bone health support cognition by enabling movement and exercise?

“The body is a system, not a collection of isolated diseases,” she highlighted.

Proteomics as a bridge between disciplines

A recurring theme in Schilling’s work is the power of proteomics to connect disciplines that rarely interact. Bone biologists, neuroscientists, and oncologists all bring distinct expertise, but proteomic data can act as common ground.

“A bone biologist would never normally go to a neuroscience conference, but proteomics lets us bring these worlds together,” she said. “Proteomics can really be a catalyst, connecting specialists who each hold a piece of the puzzle.”

Her lab is also applying these approaches to questions such as why certain cancers tend to have a preference to metastasize to bone, building collaborations with clinicians at MD Anderson and other institutions.

Proteoforms and the future of protein research

While MS continues to evolve rapidly, Schilling is equally excited by emerging non-MS approaches. In particular, she highlights the progress of Nautilus Biotechnology, a company developing a platform to profile full proteoforms. Proteoforms are different structural versions of a protein that can originate from a single gene and are formed by changes in the amino acid sequence or post-translational modifications.

It’s now possible to probe proteoforms of tau, for example, by looking at splice variants and complex phosphorylation patterns.

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“I think proteoforms, not just peptides, could reshape how we think about proteomics,” she said. Her lab has been among the first to test the Nautilus instrument outside the company.

Understanding splice variants is important for aging research, she noted, because the splicing machinery often starts to dysfunction as we age and may subsequently contribute to brain disorders and cancer.

Improving healthspan rather than increasing lifespan

As researchers dive deeper into the science of aging, public curiosity about how to live longer is growing, but does focusing on ways to extend life make sense if quality of life isn’t improved? When asked what message she would give to the average person seeking longevity advice, Schilling said: “We don’t want to extend lifespan; we want people to live healthier for longer—extending the healthspan.”

“Exercise, nutrition and good sleep matter, but so does avoiding social isolation, which can be one of the most detrimental factors in aging,” she added.

Her team’s multiomics studies of active versus sedentary older adults are beginning to uncover why physical activity makes such a difference on a molecular level. But she stresses that lifestyle alone can’t prevent every age-related disease.

“If we can intervene in basic mechanisms like senescence, we might influence many age-related conditions at once,” she said. “Studying aging helps us understand, and hopefully prevent, the earliest stages of disease.”

With thanks to Gustav Ceder, who conducted this interview on behalf of Technology Networks during HUPO 2025.

This article includes some research findings that are yet to be peer-reviewed. Results are therefore regarded as preliminary and should be interpreted as such. Find out about the role of the peer review process in research here. For further information, please contact the cited source.