# Longevity assurance interventions, metabolic health and Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $492,715

## Abstract

The mechanisms responsible for the age dependence of the onset of neurodegeneration are
unknown, which represents a fundamental problem both in neuroscience and biogerontology.
Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by
dementia, deposition of beta amyloid (Aβ) plaques, and neurofibrillary tau tangles. Despite
progress in developing treatments for the symptomatic relief of AD, most drugs only exhibit
marginal benefits and no cure currently exists. Epidemiological and preclinical studies provide
strong evidence that metabolic derangements including obesity, metabolic syndrome and type 2
diabetes constitute major risk factors for age-related diseases including dementia and AD but
the mechanisms involved remain to be elucidated.
 The GH signaling functions as a central regulator of metabolism and energy use, and it
coordinates the physiological responses of the entire organism through hormonal signaling.
Mutant animals with reduced GH signaling are not only long-lived, but are protected against
age-associated decline in memory and learning. Methionine restriction has been shown
previously to extend lifespan and delay aging in both rats and mice, dramatically decrease body
weight and adiposity, and improve insulin sensitivity and ameliorate aging-associated alterations
in glucose and lipid homeostasis. Thus, combing delaying aging models with AD disease
models exhibiting various phenotypic effects provides a novel opportunity to develop new
models that will allow studies focused on the interaction between aging, metabolism, and
neurodegeneration.
 Our proposed study will determine if suppression of the GH signaling and methionine
restriction will prevent development of behavioral, electrophysiological and histopathologic
abnormalities of AD phenotype can serve as a model to study the interaction of aging with AD,
providing a new level of analysis of the human brain in health and disease.

## Key facts

- **NIH application ID:** 9939280
- **Project number:** 5R01AG057734-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Liou Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $492,715
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939280

## Citation

> US National Institutes of Health, RePORTER application 9939280, Longevity assurance interventions, metabolic health and Alzheimer's Disease (5R01AG057734-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939280. Licensed CC0.

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