Evidence mapPaperPMID 40407975Full record

ReviewGeroScience2025

Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.

Rafal Gulej, Roland Patai, Anna Ungvari, Attila Kallai, Stefano Tarantini, Andriy Yabluchanskiy, Derek M Huffman, Michael J Conboy, Irina M Conboy, Mika Kivimäki and 2 more

Abstract readReview
In one paragraph

Review in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. A review of animal models of vascular dementia.Molecular biology reports · 2026
    Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Research progress on blood therapy for anti-aging.Journal of advanced research · 2026
    Review
  10. Article
  11. Review
  12. Senotherapeutics for Brain Aging Management.Neurology international · 2025
    Review
  13. Review
  14. Review
  15. Review
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

12 authors.

Rafal GulejVascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Roland PataiVascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Anna UngvariInstitute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. Ungann2004@gmail.com.ORCID 0009-0001-5053-2828
Attila KallaiInstitute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
Stefano TarantiniVascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Andriy YabluchanskiyVascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Derek M HuffmanDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Michael J ConboyDepartment of Bioengineering, University of California Berkeley, Berkeley, CA, 94720, USA.
Irina M ConboyDepartment of Bioengineering, University of California Berkeley, Berkeley, CA, 94720, USA.
Mika KivimäkiUCL Brain Sciences, University College London, London, UK.
Anna CsiszarVascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Zoltan UngvariVascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Funding

Tracking and Evaluation CoreU54GM104938 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$4.4M
Research Development CoreP30AG050911 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$1.3M
Chemotherapy-induced vascular cognitive impairment: role of endothelial senescenceR01CA255840 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2022 to 2025
$982k
Radiation-induced astrocyte dysfunction and cognitive declineR01NS100782 · NINDS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZOLTAN Istvan UNGVARI · 2021 to 2022
$686k
Effects of NAD restoration on neurovascular coupling in community dwelling older adultsR01AG075834 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$643k
Cerebral microhemorrhages and gait abnormalities in agingR01AG055395 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$424k
The role of IGF-1 signaling in vascular smooth muscle cells in age-related vascular cognitive impairment and dementiaR01AG070915 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$350k
Time-restricted feeding (TRF) for prevention of age-related vascular cognitive impairment and dementiaR03AG070479 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Stefano Tarantini · 2022 to 2022
$290k
Cerebral Autoregulation, Metabolic derangement, and Edema in Encephalopathy Outcome (CAMEEO)K23AG078705 · NORTHWESTERN UNIVERSITY · 2025 to 2025
$190k
Midlife Obesity, Neurovascular Senescence and Cognitive DeclineK01AG073614 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$120k
Targeting adipose tissue thermogenesis for age-related vascular cognitive impairmentK01AG073613 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$119k
American Heart Association-American Stroke Association AHA_941290Medical Research Council MR/Y014154/1NCI NIH HHS R01 CA255840NIA NIH HHS K01 AG073613NIA NIH HHS K01 AG073614NIA NIH HHS K23 AG078705NIA NIH HHS P30 AG050911NIA NIH HHS R01 AG055395NIA NIH HHS R01 AG056477NIA NIH HHS R01 AG068295NIA NIH HHS R01 AG070915NIA NIH HHS R01 AG075834NIA NIH HHS R03 AG070479NIA NIH HHS R21 AG080775NIA NIH HHS RF1 AG062553NIA NIH HHS RF1 AG072295NIGMS NIH HHS U54 GM104938NINDS NIH HHS R01 NS100782Wellcome Trust 221854/Z/20/Z
6 · The paper itself

Abstract

Aging is a complex biological process that detrimentally affects the brain and cerebrovascular system, contributing to the pathogenesis of age-related diseases like vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). While cell-autonomous mechanisms that occur within cells, independent of external signals from neighboring cells or systemic factors, account for some aspects of aging, they cannot explain the entire aging process. Non-autonomous, paracrine and endocrine, pathways also play a crucial role in orchestrating brain and vascular aging. The systemic milieu modulates aging through pro-geronic and anti-geronic circulating factors that mediate age-related decline or confer rejuvenative effects. This review explores the impact of systemic factors on cerebrovascular and brain aging, with a particular focus on findings from heterochronic parabiosis, blood exchange, and plasma transfer experiments. We discuss how these factors influence fundamental cellular and molecular processes of aging and impact cerebrovascular endothelial function, neurovascular coupling mechanisms, blood-brain barrier integrity, neuroinflammation, capillary density, and amyloid pathologies, with significant consequences for cognitive function. Additionally, we address the translational potential and challenges of modifying the systemic milieu to promote brain health and prevent age-related cognitive impairment.

Indexed as

AgingBrainParabiosisAnimalsBlood-Brain BarrierCerebrovascular CirculationHumansAgeingCerebral blood flowCerebral circulationCerebral microcirculationCerebrovascular agingEndocrineEndothelialEndothelial dysfunctionGeroscienceHumoralNeurodegenerationNeuroendocrine theoryNeuroinflammationRegulationSenescenceSystemicSystemic determinantsVascular aging

Identifiers

PMID40407975
PMCPMC12635022

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.