New in eNeuro from Wolfe et al: Brain structures related to shifting between tasks or updating information about the environment show signs of deterioration in late adulthood.

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Cognitive flexibility, a mental process crucial for adaptive behavior, involves multi-scale functioning across several neuronal organization levels. While the neural underpinnings of flexibility have been studied for decades, limited knowledge exists about the structure and age-related differentiation of the white matter subserving brain regions implicated in cognitive flexibility. This study investigated the population-level relationship between cognitive flexibility and properties of white matter across two periods of human adulthood, aiming to discern how these associations vary over different life stages and brain tracts among men and women. We propose a novel framework to study age effects in brain structure-function associations. First, a meta-analysis was conducted to identify neural regions associated with cognitive flexibility. Next, the white matter projections of these neural regions were traced through the Human Connectome Project tractography template to identify the white matter structure associated with cognitive flexibility. Then, a cohort analysis was performed to characterize myelin-related macromolecular features using a subset of the UK Biobank magnetic resonance imaging (MRI) data, which has a companion functional/behavioral dataset. We found that the wiring of cognitive flexibility is defined by a subset of brain tracts, which present undifferentiated features early in adulthood and significantly differentiated types in later life. These MRI-derived properties are correlated with individual subprocesses of cognition, which are closely related to cognitive flexibility function. In late life, myelin-related homogeneity of specific white matter tracts implicated in cognitive flexibility declines with age, a phenomenon not observed in early life. Our findings support the age-related differentiation of white matter tracts implicated in cognitive flexibility as a natural substrate of adaptive cognitive function.

Significance Statement Cognitive flexibility function facilitates adaptation to environmental demands. Brain changes affecting structural organization during the lifespan are theorized to impact cognitive flexibility. This study characterizes how the brain’s connectivity is correlated with cognitive flexibility function throughout adulthood. By analyzing myelin-related properties of white matter, this study found that certain parts of the brain’s wiring related to cognitive flexibility become more differentiated with advanced age. These age-related features appear as a natural characteristic of the human brain that may impact specific aspects of adaptive thinking, like shifting between tasks or updating information.

Researchers at the Icahn School of Medicine at Mount Sinai have characterized how cellular senescence—a biological process in which aging cells change how they function—is associated with human brain structure in both development and late life. The study, published January 22 in Cell, provides new insight into how molecular signatures of cellular senescence that are present during development and aging mirror those associated with brain volume and cortical organization.

Understanding brain structure is a central challenge in neuroscience. Although brain structure changes throughout life and is linked to both aging and neurodegenerative conditions such as Parkinson’s and Alzheimer’s diseases, the underlying molecular processes involved—including cellular senescence—are not defined. Cellular senescence is commonly defined as a state characterized by permanent cell cycle arrest in the absence of cell death, in which cells have altered function. While cellular senescence has been implicated in aging and disease, its role in shaping human brain structure—both during development and aging—has remained unclear.

“This is the first study to directly link senescence-related molecular networks in living human brain tissue to measurable differences in brain structure within the same individuals,” said Noam Beckmann, PhD, Director of Data Sciences and founding member for the Mount Sinai Clinical Intelligence Center, Assistant Professor of Artificial Intelligence and Human Health, and co-senior author of the paper. “By identifying molecular pathways that are engaged in both brain structure development and aging, our work highlights senescence as a fundamental biological feature of brain aging and neurodegenerative disease and helps prioritize targets for future experimental research aimed at protecting brain health.”

Researchers at the Icahn School of Medicine at Mount Sinai have characterized how cellular senescence—a biological process in which aging cells change how they function—is associated with human brain structure in both development and late life.

The study, published in Cell, provides new insight into how molecular signatures of cellular senescence that are present during development and aging mirror those associated with brain volume and cortical organization.

Understanding brain structure is a central challenge in neuroscience. Although brain structure changes throughout life and is linked to both aging and neurodegenerative conditions such as Parkinson’s and Alzheimer’s diseases, the underlying molecular processes involved—including cellular senescence—are not defined.

Vaccines may do far more than prevent infections.

The way that some inoculations train your immune system could also reduce the risk of cancer, stroke, or heart attacks, and possibly guard against dementia.

New evidence shows that the shingles vaccine is linked to slower aging, with benefits that can last for several years after vaccination.

Researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have found that a key protein can help to regenerate neural stem cells, which may improve aging-associated decline in neuronal production of an aging brain.

Published in Science Advances, the study identified a transcription factor in the brain, cyclin D-binding myb-like transcription factor 1 (DMTF1), as a critical driver of neural stem cell function during the aging process. Transcription factors are proteins that regulate genes to ensure that they are expressed correctly in the intended cells.

The study, led by Assistant Professor Ong Sek Tong Derrick and first author Dr. Liang Yajing, both from the Department of Physiology and the Healthy Longevity Translational Research Program at NUS Medicine, sought to identify biological factors that influence the degeneration of neural stem cell function often associated with aging, and guide the development of therapeutic approaches to mitigate the adverse effects of neurological aging.