# Delay of Alzheimer's phenotypes by interventions that increase lifespan

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $423,750

## Abstract

The purpose of the proposed project is to assess if genetic and pharmacological manipulations
that increase lifespan will similarly delay the onset of pathologies in models of Alzheimer's Disease
(AD), with the ultimate goal of developing better treatments for this devastating and expensive
disease. There are currently no effective treatments for this disease, which is on course to bankrupt
the American health system in less than 30 years, despite tremendous and expensive efforts by
pharmaceutical companies. The proposed studies take a different approach than taken by
pharmaceutical companies, which have been based on specific targets. Instead the proposed studies,
in response to NIH PAR-18-596, is based on the concept that since age is the major risk factor for AD,
and genes that produce AD in humans produce pathologies in model organisms whose time-course
scales with lifespan, manipulations that increase lifespan might also delay the onset of AD in humans.
Indeed we and others have already demonstrated that some genetic manipulations and drugs that
increase lifespan in the model organ C. elegans also delay symptoms in a standard transgenic model
of AD, and some of these discoveries have led to current clinical trials in human AD. However, only a
very small fraction of manipulations known to increase lifespan have been assessed for their effects
on impairments in models of AD. We therefore propose to address this deficiency by assessing
effects of genetic and pharmacological manipulations that reliably increase lifespan on three different
C. elegans models of AD: muscle-specific human Abeta 1-42 (standard model), and neuronal-specific
human Abeta and Tau, both implicated in human AD. We will also conversely assess if drugs we
have already discovered to protect in the muscle-specific Abeta model will also protect in the neuron-
specific models of AD and to increase lifespan. Based on the success of the small number of similar
studies which we and others have carried out, leading to clinical trials in human AD, we anticipate that
the presently proposed studies will vastly increase the available drugs and drug targets promising to
treat human AD.

## Key facts

- **NIH application ID:** 10404591
- **Project number:** 5R01AG062303-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** CHARLES V MOBBS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2018-09-30 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404591

## Citation

> US National Institutes of Health, RePORTER application 10404591, Delay of Alzheimer's phenotypes by interventions that increase lifespan (5R01AG062303-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10404591. Licensed CC0.

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