Evidence map›Paper›PMID 42282001›Full record

ArticleResearch square2026

Time-restricted feeding rejuvenates cerebrovascular function and preserves cognition during aging.

Madison Milan, Sharon Negri, Rakesh Rudraboina, Eva Troyano-Rodriguez, Jennifer Ihuoma, Aleksandra Kosmider, Shantipriya Awasthi, Woncheol Jung, Hassan Abushukair, Rohan Varshney and 15 more

Abstract readPreprint
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Madison MilanVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.ORCID 0009-0002-5078-1741
Sharon NegriVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Rakesh RudraboinaVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Eva Troyano-RodriguezVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Jennifer IhuomaVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.ORCID 0009-0008-3479-5805
Aleksandra KosmiderVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Shantipriya AwasthiOklahoma School of Science and Math, Oklahoma City, OK.
Woncheol JungDepartment of Oncology Science, University of Oklahoma Health Science, Oklahoma City, OK.ORCID 0000-0002-5473-9463
Hassan AbushukairDepartment of Oncology Science, University of Oklahoma Health Science, Oklahoma City, OK.
Rohan VarshneyDepartment of Biochemistry and Physiology, University of Oklahoma Health Science, Oklahoma City, OK.
Greg MullenDepartment of Biochemistry and Physiology, University of Oklahoma Health Science, Oklahoma City, OK.
Raghavendra Yelahanka NagarajaVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Niharika UppariVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Mohiuddin AhmadDepartment of Cell Biology, University of Oklahoma Health Science, Oklahoma City, Oklahoma.
Priya BalasubramanianVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Shannon ConleyVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Andriy YabluchanskiyVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Anna CsiszarVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Zoltan UngvariVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Audrey CleurenDepartment of Cell Biology, University of Oklahoma Health Science, Oklahoma City, Oklahoma.
Michael RudolphDepartment of Biochemistry and Physiology, University of Oklahoma Health Science, Oklahoma City, OK.
Mickael TanterInstitute Physics for Medicine Paris, INSERM U1273, ESPCI PSL Paris, CNRS UMR 8631, PSL Research University, Paris, France.
Tae Gyu OhStephenson Cancer Center, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.
Rafael de CaboTranslational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0002-3354-2442
Stefano TarantiniVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Science, Oklahoma City, Oklahoma, USA.

Funding

Tracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Janis E Campbell · 2013 to 2026
$68.2M
Tissue Pathology Shared ResourceP30CA225520 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ROBERT S. MANNEL · 2018 to 2026
$27.1M
Visualizing insulin actions on neuronal metabolism and function using fluorescent biosensorsP20GM125528 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI David M Sherry · 2019 to 2026
$17.8M
Targeted DNA Methylation and Mitochondrial Heteroplasmy CoreP30AG050911 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Matthew John Hart · 2015 to 2026
$13.9M
Cerebral microhemorrhages and gait dysfunction in agingR01AG055395 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA · 2017 to 2025
$2.3M
Age-related vascular cognitive impairment: role of endothelial senescenceR01AG068295 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA, UNGVARI, ZOLTAN ISTVAN · 2020 to 2024
$1.8M
The role of IGF-1 signaling in vascular smooth muscle cells in age-related vascular cognitive impairment and dementiaR01AG070915 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CONLEY, SHANNON M · 2021 to 2025
$1.8M
Radiation-induced astrocyte dysfunction and cognitive declineR01NS100782 · NINDS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI UNGVARI, ZOLTAN ISTVAN · 2018 to 2022
$1.7M
Chemotherapy-induced vascular cognitive impairment: role of endothelial senescenceR01CA255840 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA · 2021 to 2025
$1.6M
Cerebromicrovascular rejuvenation by heterochronic blood exchangeR01AG072295 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA, UNGVARI, ZOLTAN ISTVAN · 2024 to 2025
$875k
Midlife Obesity, Neurovascular Senescence and Cognitive DeclineK01AG073614 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI TARANTINI, STEFANO · 2021 to 2025
$601k
Targeting adipose tissue thermogenesis for age-related vascular cognitive impairmentK01AG073613 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI BALASUBRAMANIAN, PRIYA · 2021 to 2025
$596k
American Heart Association-American Stroke Association 24TPA1299954American Heart Association-American Stroke Association 25IPA1456700NCI NIH HHS P30 CA225520NCI NIH HHS R01 CA255840NIA NIH HHS K01 AG073613NIA NIH HHS K01 AG073614NIA NIH HHS P30 AG050911NIA NIH HHS R01 AG055395NIA NIH HHS R01 AG068295NIA NIH HHS R01 AG070915NIA NIH HHS R01 AG072295NIA NIH HHS R03 AG070479NIA NIH HHS R21 AG080775NIGMS NIH HHS P20 GM125528NIGMS NIH HHS U54 GM104938NINDS NIH HHS R01 NS100782
6 · The paper itself

Abstract

Cerebromicrovascular dysfunction is a key driver of age-related cognitive decline, yet interventions targeting microvascular aging remain limited. Here, we show that time-restricted feeding (TRF) preserves cognitive function and rejuvenates cerebrovascular physiology in aged mice. TRF improves resting cerebral blood flow and neurovascular coupling while attenuating blood-brain barrier disruption, neuroinflammation, and endothelial senescence. Mechanistically, TRF enhances metabolic flexibility and restores mitochondrial bioenergetic capacity in cerebromicrovascular endothelial cells. Ketone bodies elevated by TRF recapitulate key mitochondrial and vascular effects, improving endothelial respiration, membrane potential, and redox balance in aged mice and primary human brain endothelial cells, but do not fully reproduce neurovascular unit protection. These findings identify endothelial mitochondrial reprogramming as a central mechanism linking dietary timing to cerebrovascular resilience and cognitive preservation, and suggest that metabolic interventions can partially reverse key features of vascular brain aging.

Indexed as

AgingBlood–brain barrierCerebrovascular agingCognitive declineEndothelial metabolismKetone bodiesMetabolic reprogrammingMitochondrial functionNeurovascular couplingTime-restricted feeding

Identifiers

PMID42282001
PMCPMC13252521

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.