# AGING BIOMARKER--CARDIAC NOREPINEPHRINE

> **NIH NIH R01** · ALLEGHENY UNIVERSITY OF HEALTH SCIENCES · 1993 · $146,746

## Abstract

Investigations by the P.I. have demonstrated an age-related decrease in
norepinephrine (NE) release at the cardiac neuroeffector junction.  The
pattern of alterations in NE release is gender dependent.  Changes in
cardiac adrenergic nerve function may provide a useful biomarker of the
aging process in both sexes.  We are proposing studies which will 1)
establish uptake and release of NE and the NE analog
metaiodobenzylquanidine (MIBG) from cardiac adrenergic nerves as
biomarkers of aging, 2) elucidate the physiologic and molecular
mechanisms for the age-related reduction in NE release and the capacity
of dietary restriction (DR) and gender to influence NE release, and 3)
non-invasively measure age-related changes in adrenergic control of the
heart by scintigraphic imaging of the uptake and release of radiolabeled
MIBG from cardiac adrenergic nerve terminals in the whole animal.  We
have found the reduction in NE release is related to a decrease in
function of neuronal calcium channels.  Prolongation of life span by DR
may be due in part to preserving the integrity of neuronal calcium
channels during aging and promoting the availability of calcium to
stimulate exocytotic release of NE.  To explore this hypothesis and to
carry out the studies cited above we will use cardiac synaptosome
preparations (a technique developed in the P.I.'s laboratory) which
permit a molecular approach to the study of adrenergic neurotransmission.
NE and MIBG uptake and potassium-induced NE and MIBG release from cardiac
synaptosomes will be determined at 6, 12, 18 and 24 months of age in ad
lib. and DR fed Fischer 344 and Brown Norway (BN) rats of both sexes.  BN
is being studied to determine that the results are not strain dependent.
We believe these studies will establish NE and MIBG uptake and release as
reliable, reproducible, and sensitive biomarkers of aging.  The molecular
mechanisms responsible for changes in NE release as a function of DR, age
and gender will be examined in cardiac synaptosomes by using
pharmacological probes which affect calcium channel function and NE
release, and by determining the kinetics of 45-Ca2+ movement through
neuronal Ca2+ channels.  Radiolabeled MIBG will be injected into rats and
scintigraphic imaging will be used as a non-invasive means of estimating
NE uptake and turnover as a function of DR, age, and gender.  We believe
that these studies will lead to the development of MIBG uptake and
release in the human heart as a valid biomarker for testing future
interventions in the aging process.

## Key facts

- **NIH application ID:** 3123051
- **Project number:** 1R01AG011060-01
- **Recipient organization:** ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
- **Principal Investigator:** JAY ROBERTS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $146,746
- **Award type:** 1
- **Project period:** 1993-05-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123051

## Citation

> US National Institutes of Health, RePORTER application 3123051, AGING BIOMARKER--CARDIAC NOREPINEPHRINE (1R01AG011060-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123051. Licensed CC0.

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