UTHealth Houston Scientist Wins $12 Million to Probe Brain Energy and Aging

A sweeping new effort to understand why some brains stay sharp while others falter with age has received a major financial boost. Rima Kaddurah-Daouk, PhD, professor and chair of the Department of Precision Behavioral Health at UTHealth Houston School of Behavioral Health Sciences, has secured a five-year, $12 million grant from the National Institute on Aging to investigate how changes in the brain’s energy supply shape memory, mood, and the risk of Alzheimer’s disease. The award, announced on 14 October 2026, funds a collaborative initiative that will pursue one of the most fundamental questions in healthy aging: what allows the brain to remain resilient, and how can that knowledge be translated into better ways to protect brain health throughout life?

At the center of the project sits a tiny but indispensable piece of cellular machinery: the mitochondrion. These organelles act as the power plants of cells, converting sugars and fats into the chemical energy that fuels everything a neuron does. The brain is an extraordinarily expensive organ to run, consuming a disproportionate share of the body’s energy relative to its size, and it depends almost entirely on the efficient, continuous output of mitochondrial metabolism. When that output falters, neurons are among the first cells to suffer, which is why researchers have increasingly suspected that impaired cellular energy metabolism lies upstream of many of the most devastating disorders of aging.

The evidence supporting that suspicion has accumulated steadily over the past decade. Large initiatives funded by the National Institute on Aging, particularly those generating multiomics data that combine genomics, metabolomics, and other molecular measurements, have produced growing evidence that mitochondrial function and efficient energy production are central to mechanisms of resilience during aging. Impaired energy metabolism has been linked not only to Alzheimer’s disease but also to depression, anxiety, and broader cognitive decline. The new initiative will investigate how mitochondrial dysfunction contributes to these conditions, and, just as importantly, why some individuals maintain resilience while others become more susceptible as they grow older.

The molecular insights generated by the project are intended to do more than describe the problem. By pinpointing the pathways through which failing energy metabolism erodes brain function, the researchers hope to develop therapeutic approaches that sustain or increase resilience during aging and protect cognitive function over the long term. In this sense, the grant represents a deliberate push to move mitochondrial biology out of the laboratory and toward interventions that could one day be offered to patients, whether in the form of drugs, supplements, or precisely targeted lifestyle changes.

The work builds on decades of leading research by the Alzheimer Disease Metabolomics Consortium, part of the Accelerating Medicines Partnership Program for Alzheimer’s Disease, a public-private effort that has transformed how researchers think about the molecular fingerprints of the disease. One of the consortium’s key strategies has been to look for measurable changes in blood that can provide insight into cellular energy failures within the brain. If blood-based markers can reliably reflect what is happening inside the brain’s energy systems, they could offer researchers and clinicians a noninvasive window onto aging itself, opening the door to earlier detection and better monitoring of therapeutic response.

To that end, the research team will profile blood samples from large Alzheimer’s disease and community cohorts, searching for distinct metabolomic signatures in men and women that serve as proxies for mitochondrial health and function. Metabolomics, the systematic measurement of the small molecules produced by cellular metabolism, is uniquely suited to this task because metabolic byproducts shift rapidly and measurably when energy production is disrupted. Through longitudinal analysis, the team will determine how these peripheral blood markers correlate with Alzheimer’s disease progression over time, tracking whether specific metabolic patterns predict decline years before symptoms appear. A central focus of this analysis will be the evaluation of sex-driven differences, an area of growing importance in Alzheimer’s research given that the disease affects women disproportionately and that emerging evidence suggests men and women may follow different biological routes to the same pathology.

The initiative will not stop at observational associations. The project will also examine how genetics and lifestyle factors influence mitochondrial dysfunction, and it will deploy advanced cell-based systems, chemical screening, and genetic screening to map direct functional links between mitochondrial failure and Alzheimer’s disease pathology. This combination of approaches allows the team to move beyond correlation and toward causation: if disrupting a particular metabolic pathway in cells produces hallmark features of Alzheimer’s pathology, and if restoring that pathway reverses them, researchers gain a much stronger basis for designing interventions. The explicit attention to sex differences at this mechanistic level reflects a broader shift in the field toward precision medicine that accounts for biological variation between patient groups rather than treating the disease as a single entity.

Importantly, the research is designed from the outset to move from discovery toward potential applications. By screening compounds that target mitochondria, the team will investigate potential drug and supplement approaches, as well as lifestyle changes, that could collectively enable more efficient energy production and support brain health. The logic is straightforward: if declining mitochondrial efficiency is a shared thread running through memory loss, mood disorders, and dementia risk, then bolstering that efficiency could yield benefits across multiple dimensions of brain aging simultaneously. Whether such interventions will ultimately prove effective in people remains an open question, but the grant provides the infrastructure to identify the most promising candidates systematically rather than by trial and error.

For Kaddurah-Daouk, the award carries both scientific and institutional significance. It marks the first National Institutes of Health award presented to her since she joined UTHealth Houston in July 2026, and it adds to a rich grant portfolio she transferred to the institution. The grant represents an important expansion of UTHealth Houston’s growing focus on brain health, and Kaddurah-Daouk joins the university with the support of a new endowed chair funded by the John S. Dunn Foundation. In a statement accompanying the announcement, she framed the work in explicitly translational terms: by uncovering the distinct pathways through which mitochondria fail in men and women, she said, the team is paving the way for novel precision medicine approaches for the prevention and treatment of Alzheimer’s disease that account for differences between men and women.

The scale of the collaboration underscores how ambitious the undertaking is. In addition to working with other National Institute on Aging-funded consortia, Kaddurah-Daouk and her team will partner with researchers at Mayo Clinic, the Icahn School of Medicine at Mount Sinai, the University of Washington, UNC Chapel Hill, the University of Kansas Medical Center, Purdue University, Sage Bionetworks, the Baker Heart and Diabetes Institute, and Helmholtz Zentrum München, among other leading research institutions. Matthias Arnold, PhD, of Helmholtz Zentrum München, and Russell Swerdlow, MD, of the University of Kansas, will serve as principal investigators alongside Kaddurah-Daouk. Bringing together metabolomics experts, clinical cohorts, computational biologists, and drug-screening facilities across multiple continents, the initiative aims to turn one of biology’s oldest questions, how the brain keeps its lights on, into a concrete roadmap for keeping them on longer. If the five-year program succeeds in linking blood-borne metabolic signatures to brain energy failure and identifying compounds or lifestyle strategies that restore resilience, it could reshape how scientists and physicians approach the prevention of Alzheimer’s disease and age-related cognitive decline, shifting the emphasis from treating damage after it occurs to protecting the brain’s energy systems before they fail.

Subject of Research: Mitochondrial energy metabolism as a driver of resilience, memory, mood, and Alzheimer's disease risk during brain aging

Article Title: Kaddurah-Daouk secures $12 million grant to advance brain health research

Article References: Kaddurah-Daouk secures $12 million grant to advance brain health research. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: mitochondria, brain energy metabolism, Alzheimer's disease, aging, metabolomics, precision medicine, National Institute on Aging, UTHealth Houston, blood biomarkers, sex differences, cognitive decline, resilience