# Midlife Obesity, Neurovascular Senescence and Cognitive Decline

> **NIH NIH K01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2022 · $120,156

## Abstract

Stefano Tarantini, PhD, is a junior aging researcher whose overarching goal is to develop an independent
research program to understand and apply nutritional lifestyle interventions to the field of cerebrovascular aging
to ameliorate age-related vascular cognitive impairment and dementias (VCID). To achieve this, the following
K01 proposal aims to further Dr. Tarantini's training to enable him to explore the role of midlife obesity on
neurovascular senescence as it relates to the development of vascular cognitive impairment and related
dementias. Candidate: Dr. Tarantini is an Assistant Professor in the Dept. of Biochemistry and Molecular Biology
at the University of Oklahoma HSC. This K01 proposal perfectly builds on his previous training and extends his
research in a logical direction that is becoming growingly relevant in the field of cognitive aging. This proposal
identifies 5 training goals: 1) Acquire novel training in the field of nutrition; 2) Receive training in data integration,
biostatistics, single-cell transcriptomics, and analysis; 3) training in advanced intra-vital imaging techniques; 4)
Improve skills in magnetic resonance imaging (MRI); 5) Establish and lead an independent research laboratory.
Mentors/Environment: The mentoring team will assist the candidate to ensure his success through the K01
training and research activity. The proposed plan will leverage resources of the newly established Center for
Geroscience and Healthy Brain Aging, the NIH supported Nathan Shock Center, and the NIGMS-funded CoBRE
training grant. The department is fully committed to support Dr. Tarantini independently of the outcome of this
K01 application. Research: Mid-life obesity promotes cellular senescence. Aging-induced senescence among
cells of neurovascular unit (NVU) associates with neurovascular dysfunction and cognitive impairment. Yet, the
impact of obesity-induced senescence on the cellular components of the NVU and its function is not understood.
We hypothesize that obesity accelerates NVU senescence, impairing structural and functional qualities of the
cerebral vasculature. The resulting decline in cerebral blood flow and increased neuroinflammation contribute to
cognitive impairment. We predict that elimination of senescent cells rejuvenates the NVU, restoring its youthful
functional and structural integrity, which confers cognitive benefits. This project aims to characterize mid-life
obesity-induced senescence in the neurovascular unit (Aim 1), the effects of senescence on NVC responses,
cerebral blood flow and cognition (Aim 2), and how senescence alters microvascular density and BBB integrity
in mouse models of mid-life obesity (Aim 3). Summary: This K01 proposal utilizes advanced imaging and
sophisticated sequencing and data integration techniques in a relevant model of mid-life obesity to detect
senescence in the NVU of the brain. Understanding the relationship between brain cellular senescence and
impaired BBB function and diminishe...

## Key facts

- **NIH application ID:** 10458047
- **Project number:** 5K01AG073614-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Stefano Tarantini
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $120,156
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458047

## Citation

> US National Institutes of Health, RePORTER application 10458047, Midlife Obesity, Neurovascular Senescence and Cognitive Decline (5K01AG073614-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458047. Licensed CC0.

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