Metabolism research is a fast-moving field fueled by advances in technology and interdisciplinary collaboration.
In labs here at Van Andel Institute (VAI) and institutions around the world, scientists are making discoveries that simply weren’t possible a few years ago. This progress is possible thanks to technical innovation and team-based science, which combine leading-edge capabilities with expertise across fields to reshape what we know about diet, nutrition, and the many ways metabolism influences health and disease.
This work is far from just an academic pursuit — better understanding of metabolism has the power to help us more effectively support health, improve quality of life, and prevent and treat disease. That’s why, in 2021, we launched VAI’s Metabolism and Nutrition (MeNu) Program, a collaborative effort to understand the impact of diet and nutrition on a molecular level. The program is home to the MeNu Consortium, which brings together leading scientists across the spectrum of metabolism research.
This spring, Consortium members met at VAI to identify opportunities for the next big breakthroughs in metabolism. The criteria were simple: ideas must be bold, impactful and primed for discovery. The team identified six areas, detailed below, that are ripe for influential breakthroughs and challenge us to be creative and forward-thinking in our science. We hope that they will serve as a springboard for collaboration-driven discovery that advances the field and offers new paths for improving health.
Exercise, aging and muscle maintenance
Maintaining muscle mass is a major aspect of extending healthspan, both boosting muscle formation and blocking muscle loss. Unfortunately, several factors compete with our goal to maintain muscle mass, leaving us with an important question: How can we leverage metabolism to preserve lean muscle and vitality as we age? The MeNu Consortium predicts that this area will be a key focus over the next three to five years, with an emphasis on exploring strategies to support muscle strength and resilience. We anticipate research in this area will focus on:
- Medication-related muscle loss: Several medications on the market — including GLP-1 agonists and metformin — have transformed standard of care and quality of life for people with diabetes and obesity. Both medications work by interacting with key aspects of metabolism: GLP-1 agonists mimic a hormone that helps manage hunger and blood sugar levels while metformin slows the body’s ability to make sugar in the liver and regulates blood sugar levels. In addition to treating symptoms, however, some people who use these medications can experience decreased muscle mass. If we can identify the relationship between these medications and muscle loss, we might be able to fine-tune treatment regimens to help people control diabetes while also maintaining muscle tone.
- Age-related muscle loss: As we age, our bodies lose muscle, which affects strength, mobility and day-to-day function. Muscle loss also increases the risk of falls and fractures. Inactivity and metabolic disorders such as diabetes are linked to a greater risk for muscle loss while healthy diets and routine exercise are linked to slower muscle loss with age. Although we have clues as to why we lose muscle as we age, we don’t yet have solutions as to how to best maintain muscle mass throughout the aging process. Identifying specific metabolic processes underlying age-related muscle loss could inform new targeted diets or therapies to halt or reverse muscle loss.
Molecular mechanisms that link nutrition to better health
Science-backed diets can be important parts of treatment plans for many diseases, including Crohn’s disease, epilepsy and some cancers. However, restrictive diets can be difficult to maintain long-term. Understanding exactly how these diets work on a molecular level could lead to new drug-based therapies for supporting health and managing and treating disease.
The MeNu Consortium predicts this will be a fast-moving area, with researchers eager to explore the molecular links between diet, health and disease to enable development of new strategies based on rigorous, sound science.
Dietary changes and medical decisions should be discussed with your health care provider.
Mechanisms linking metabolism to epigenetic programming
Epigenetics are like notes written in the margins of our DNA. Epigenetic notes, or “marks,” change how the instructions in our DNA are read and used without changing the DNA sequence itself. Some epigenetic marks can protect us from disease while others can predispose us to it. Because they can be “written” or “erased,” epigenetic marks offer potentially powerful therapeutic opportunities.
Metabolism and nutrition affect epigenetics, but the precise details remain unclear. Understanding this relationship offers a promising frontier for discovery. The MeNu Consortium anticipates a focus on:
- Metabolism’s influence on the writers and erasers of epigenetic notes: Gene expression is the process by which the instructions in a gene are used to create proteins, the molecular workhorses of the body. Some of these proteins are specifically tasked with writing and/or erasing epigenetic notes (marks). If something goes wrong and writers or erasers become lost or dysfunctional, the consequence can be disease. Metabolism and gene expression have a tight relationship: metabolism provides the energy needed for gene expression while gene expression enables production of the proteins required for metabolic function.
- Metabolites are the “ink” of epigenetics: To write an epigenetic note (mark) in the margins of DNA, special kinds of “ink” are needed, with different types of ink used to “write” different types of epigenetic notes. Metabolism helps make these epigenetic inks, meaning that if we aren’t eating the right foods or our metabolism isn’t working correctly, the ink can potentially run out. Without the right ink, our body can’t write its epigenetic notes and may not know how to correctly interpret DNA instructions.
- Cell differentiation: Cell differentiation occurs when immature, unspecialized cells take on a specific function, such as becoming an immune cell or a bone cell. This process is governed by epigenetic notes (marks), which help each cell use and act upon the right instructions in DNA at the right time. If the wrong epigenetic notes are scribbled in the margin, immature cells can take on the wrong function. Or if the correct epigenetic notes are missing, immature cells don’t take on the functions that the body needs. Thanks to advances in technology, we can better study how nutrients and metabolic processes support the writing and erasing of specific epigenetic notes. These insights may inform new ways to help the body better function, such as developing strategies to strengthen bone or reduce inflammation.
- Intergenerational inheritance: Intergenerational inheritance is a growing field that explores how parental diet and environmental exposures can influence the health of offspring via epigenetics, which can be passed from parent to child during development. Several VAI researchers already work in this area. The MeNu Consortium predicts this field will take off, with a focus on defining which epigenetic notes can be passed to offspring and their effect on the health of the next generation.
Learn more about the MeNu Program ➔
Spatial and subcellular metabolic analysis
Technology is the bread and butter of metabolism research and will remain a major driver of innovation in the coming years. MeNu-supported teams are actively developing spatial metabolomics, rapid cell isolation and targeted metabolite delivery methods to reveal how metabolism acts within specific cells. The MeNu Consortium also is curious and cautiously enthusiastic about the possibilities of leveraging artificial intelligence to facilitate deeper and more efficient metabolism research.
Exploring organ-specific metabolism
Just as every part of the body plays a vital and unique role, so too do the unique metabolic profiles of different organs. From brain to muscle to liver, MeNu-supported researchers are mapping organ-specific metabolic processes, which the Consortium predicts will unlock new opportunities for precision therapies.
Understanding metabolic regulation of development — from cells to organisms
From the earliest stages of life, metabolism drives (or inhibits) development. The MeNu Consortium expects this area will be rich for future discovery, as researchers investigate how metabolic processes shape cell differentiation, tissue formation and lifelong health.
This is just a snapshot of what’s next in metabolism research. To learn more about the future of the field, join us for Horizons in Metabolism: Cell-Specific Metabolism on June 2, 2026. This one-day symposium will feature talks at the leading edge of mechanistic single cell metabolism research with an eye toward technology development and clinical implications. The symposium will focus on big questions, explore the latest research and provide ample opportunities for networking. Learn more at here.
ABOUT THE AUTHORS
Dr. Kelsey Williams joined VAI in 2018 as a scientific project leader in the lab of Dr. Russell Jones, bringing experience in mass spectrometry, data visualization and project management. In 2021, she became the scientific program manager for the Institute’s Metabolism and Nutrition (MeNu) Program. In this role, Kelsey has sustainably increased the efficiency and quality of metabolism research at VAI, facilitating new collaborations and improving grant and paper submissions. She holds a Ph.D. in fiber and polymer science from North Carolina State University and is pursuing her MBA from Indiana University.
Dr. Russell Jones is chair of VAI’s Department of Metabolism and Nutritional Programming and director of the MeNu Program. His lab investigates metabolism at the cellular level to understand how it affects cell behavior and health, with a specific eye on cancer and the immune system. By revealing how cancer cells use metabolic processes to fuel their growth and spread, Dr. Jones hopes to develop new treatments that help patients by changing the standard of care for cancer.