Landmark Living Brain Study Published in CELL Identifies a Novel Molecular Roadmap Governing Human Brain Aging

Mount Sinai and BPGbio scientists uncover novel molecular drivers from live brain samples that direct human brain structure and function from early development through aging:

• Creates a completely new molecular understanding of live aging human brain
• Reveals cellular senescence as a key component of brain structure and degeneration
• Marks a new era for precision therapies for neurodegenerative diseases, including Alzheimer’s and Parkinson’s
• Validates a large-scale living-human brain platform, advancing the shift from postmortem to living human tissue in neurological disease research

NEW YORK and BOSTON, Feb. 02, 2026 (GLOBE NEWSWIRE) --  A groundbreaking study published today in the journal CELL and led by researchers from the Living Brain Project at the Icahn School of Medicine at Mount Sinai with support from BPGbio has revealed that cellular senescence—a process long viewed as a passive biological marker of aging—is in fact an active, regulated biological program that shapes the structure of the human brain across an individual’s lifespan.

Using living cortical brain tissue collected from 141 neurosurgical patients during routine deep brain stimulation surgeries, combined with MRI imaging and advanced multi-omics analyses through Mount Sinai’s landmark Living Brain Project, the team produced the first direct molecular map connecting living cellular biology to human brain architecture.

Analyzing more than 100,000 individual cells, the researchers created a “cellular GPS” for the molecular roadmap of the aging brain—tracing how the activity of distinct cell types influences brain structure, adaptation, and degeneration.

“For generations, scientists have relied on postmortem tissue to study brain disorders,” said Alexander Charney, M.D., Ph.D., Director, The Charles Bronfman Institute for Personalized Medicine and Vice Chair, Windreich Department of Artificial Intelligence and Human Health and co-lead of The Living Brain Project at the Icahn School of Medicine at Mount Sinai, and co-senior author. “By leveraging an invaluable resource, live brain specimens obtained from routine procedures, coupled with not just one layer of biology, genomics, but multiomics we were able to interrogate living human brain tissue at a scale and depth never before possible. This approach connects molecular activity directly to brain structure, setting the stage for a new era of biologically informed therapeutic strategies based on the molecular function of specific cell types.”

The preservation of molecular integrity in live brain provides unprecedented insight into brain function. The resulting large-scale dataset offers a blueprint for understanding how molecular activity drives brain aging—and is now poised to be mined by BPGbio’s causal AI platform NAi® to uncover new therapeutic targets for neurodegenerative diseases.

“This is the first study to directly link senescence–related molecular networks in living human brain tissue to measurable changes in brain structure within the same individuals,” said Noam Beckmann Ph.D., Director of Data Sciences and founding member for the Mount Sinai Clinical Intelligence Center and co-senior author. “We show that this relationship is present across the human lifespan, from development through aging, highlighting senescence as a fundamental biological feature of brain aging and neurodegenerative disease.”

Study Design

The research analyzed living cortical brain tissue from 141 neurosurgical patients, integrating advanced molecular and imaging techniques to uncover how cellular programs shape brain structure. Using a multi-omics framework—combining bulk RNA sequencing, proteomics, and single-nucleus RNA sequencing—the team mapped gene and protein activity within specific cell types, including excitatory neurons and microglia. Each molecular dataset was paired with MRI-derived measures of cortical volume, area, and thickness, allowing researchers to construct the first molecular–structural map of the living human brain.

“This study is the latest of many recently published studies that sheds light on why the Living Brain Project is so critical, considering the tens of billions of dollars spent annually by the pharmaceutical industry in neuroscience research yet little progress has made in the area so far,” said Michael A. Kiebish, Ph.D., VP of Platform and Translational Sciences at BPGbio and co-author. “By directly accessing and characterizing living human brain tissue at multiple molecular levels, we’re not only challenging long-held assumptions about brain aging, but we’re also creating a dataset that opens entirely new avenues to identify targets and biomarkers for precision therapies for neurodegenerative diseases such as Alzheimer’s and Parkinson’s.”

Key Discoveries:

• Cellular senescence as a developmental regulator: Senescence-related gene activity in excitatory neurons correlates with smaller cortical volumes, suggesting a dual role in shaping and remodeling brain architecture.
• Shared biology between development and aging: The study identifies molecular programs active during brain formation that reemerge in older age, establishing a continuous biological thread linking growth, maintenance, and decline.
• First living-tissue molecular–structural map: By integrating living tissue, MRI, and multi-omics data, researchers provide the first view of how molecular processes shape brain structure.
  

“The Living Brain Study represents a historical landmark in medicine, potentially positioning living human brain as the primary biological reference for therapeutic innovation,” said Niven R. Narain, Ph.D., President and CEO of BPGbio. “Advances in technology now make it possible to study living human brain biology directly. With neurodegenerative disease representing a rapidly growing ~$750 billion global market, we see a significant opportunity to partner with industry leaders to translate these insights into transformative therapies.”

A New Era for Translational Neurodegenerative Disease Research

“For decades, neurological disease R&D has struggled not for lack of investment, but because it has relied on models that fail to capture how the human brain truly functions and ages,” said John Beeler, Ph.D., SVP, Business Development at BPGbio. “High attrition will persist until neurological disease research is grounded in living human tissue, aging-linked biology, cross-cellular integration, and causal models that distinguish true biological drivers from downstream correlations.”

Disclosure: Eric J. Nestler, M.D., Ph.D., Dean of the Icahn School of Medicine at Mount Sinai, was involved in this project as a thesis adviser for lead study author Anina Lund, PhD, a former neuroscience graduate student and now postdoctoral fellow at the Icahn School of Medicine.  He had no decision-making authority over experiments. Dr. Nestler also serves on BPGbio’s Scientific Advisory Board in a compensated advisory capacity.

Media Contact: media@bpgbio.com

About BPGbio, Inc.
BPGbio is a biology-first AI-powered biopharma company focused on mitochondrial biology and protein homeostasis. Headquartered in greater Boston, the company leverages its NAi Interrogative Biology® platform and one of the world’s largest clinically annotated biobanks to develop a deep pipeline in oncology, rare diseases, and neurology.

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