# EFFECTS OF HDL CHOLESTEROL LEVELS ON AGING

> **NIH NIH R01** · JACKSON LABORATORY · 1992 · $234,907

## Abstract

The objective of this proposal is to test the hypothesis that elevated
levels of plasma high density lipoprotein cholesterol (HDL-C) are able to
retard aging processes by slowing age-related physiological and
pathological changes.  Previously, only reduced caloric intake produced
these effects in mammalian models.  In humans, elevated HDL-C levels have
been shown to be cardioprotective and to extend life expectancy.  However,
the increase in longevity is greater than what might be expected from
protection against heart disease alone.  Because human population studies
are often complex and results difficult to interpret, we propose to test
the effects of HDL-C on aging in a set of newly created mouse models which
have widely differing HDL-C levels when fed a standard mouse diet.  These
models have been created in the same genetic background strain, B6
(C57BL/6J).

Five mouse strains to be used, listed in the order of decreasing HDLC
levels, are: (1) transgenic B6 mice with a human APOA1 gene, which
expresses human apoA1 at twice normal mouse levels, thereby increasing
HDL-C levels two-fold, (2) congenic B6.H Ath-lr, carrying an allele from
strain C3H, which causes atherosclerosis resistance by increasing HDL-C
levels, (3) B6, the standard aging inbred mouse model, (4) transgenic B6
mice carrying the CETP gene, which expresses cholesterol ester transfer
protein (CETP), the carrier protein that transfers cholesterol from HDL to
other lipoproteins thereby decreasing HDL-C levels, and (5) intercrossed
transgenic B6 CETP and B6APOA1 mice.  These strains have plasma HDL-C
levels of 120, 90, 60, 30, and 15 mg cholesterol/dl, respectively.

The specific hypothesis that we will test in these mice are as follows.
Hypothesis 1: With higher HDL-C levels, longevity will increase and the
rates of age-related changes in biological markers (e.g. immune system,
collagen denaturation, renal function) will be retarded.  Hypothesis 2:
With higher HDL-C levels, incidences of tumors and other pathological
biomarkers of age will be reduced.  Males and females will be compared for
both hypotheses 1 and 2, because of gender differences in tumor types and
to shed light on whether higher HDL-C levels in human females contribute to
their greater longevity.  Hypothesis 3: Low calorie diets, which retard
aging, act by mechanisms independent of the HDL-C effects.  This hypothesis
predicts that aging will be retarded to a similar extent in mice of high,
medium or low HDL-C levels fed low calorie diets.

Lifestyle changes and therapies which elevate HDL-C levels may result in a
healthier old age, if HDL-C levels play a role in retarding aging
processes.

## Key facts

- **NIH application ID:** 3122801
- **Project number:** 1R01AG010838-01
- **Recipient organization:** JACKSON LABORATORY
- **SAM.gov UEI:** XR6LMXNKDJJ1
- **Principal Investigator:** DAVID E HARRISON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $234,907
- **Award type:** 1
- **Project period:** 1992-09-15 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122801

## Citation

> US National Institutes of Health, RePORTER application 3122801, EFFECTS OF HDL CHOLESTEROL LEVELS ON AGING (1R01AG010838-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122801. Licensed CC0.

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