NEW YORK and BOSTON — February 2, 2026 — Leads & Copy — A new study reveals that cellular senescence shapes the structure of the human brain across an individual’s lifespan. The research, published in the journal CELL, was led by scientists from the Living Brain Project at the Icahn School of Medicine at Mount Sinai, with support from BPGbio.
The study challenges the view of cellular senescence as merely a passive biological marker of aging, identifying it as an active, regulated biological program.
Researchers analyzed living cortical brain tissue from 141 neurosurgical patients during routine deep brain stimulation surgeries. This was combined with MRI imaging and advanced multi-omics analyses through Mount Sinai’s 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 to create a “cellular GPS” for the aging brain.
Alexander Charney, M.D., Ph.D., Director of The Charles Bronfman Institute for Personalized Medicine, Vice Chair of the Windreich Department of Artificial Intelligence and Human Health, co-lead of The Living Brain Project at the Icahn School of Medicine at Mount Sinai, and co-senior author, stated that the team was able to interrogate living human brain tissue at an unprecedented scale and depth. He said this approach connects molecular activity directly to brain structure, setting the stage for 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. BPGbio’s causal AI platform NAi® is poised to mine the resulting large-scale dataset to uncover new therapeutic targets for neurodegenerative diseases.
Noam Beckmann Ph.D., Director of Data Sciences and founding member for the Mount Sinai Clinical Intelligence Center and co-senior author, said that the study is the first to directly link senescence–related molecular networks in living human brain tissue to measurable changes in brain structure within the same individuals. He added that the relationship is present across the human lifespan, highlighting senescence as a fundamental biological feature of brain aging and neurodegenerative disease.
The research integrated advanced molecular and imaging techniques to uncover how cellular programs shape brain structure. A multi-omics framework was used combining bulk RNA sequencing, proteomics, and single-nucleus RNA sequencing to map 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.
Michael A. Kiebish, Ph.D., VP of Platform and Translational Sciences at BPGbio and co-author, said the study sheds light on why the Living Brain Project is so critical. By directly accessing and characterizing living human brain tissue at multiple molecular levels, Kiebish noted, they are challenging long-held assumptions about brain aging and creating a dataset that opens new avenues to identify targets and biomarkers for precision therapies for neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
Key discoveries include:
- Cellular senescence as a developmental regulator: Senescence-related gene activity in excitatory neurons correlates with smaller cortical volumes.
- Shared biology between development and aging: Molecular programs active during brain formation reemerge in older age.
- First living-tissue molecular–structural map: Researchers provide the first view of how molecular processes shape brain structure.
Niven R. Narain, Ph.D., President and CEO of BPGbio, stated that the Living Brain Study represents a historical landmark in medicine, potentially positioning living human brain as the primary biological reference for therapeutic innovation. With neurodegenerative disease representing a rapidly growing ~$750 billion global market, he sees a significant opportunity to partner with industry leaders to translate these insights into transformative therapies.
John Beeler, Ph.D., SVP, Business Development at BPGbio, said that neurological disease research and development has struggled because it has relied on models that fail to capture how the human brain truly functions and ages.
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.
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.
Source: BPGbio
