# PENTOSIDINE AS A BIOMARKER OF AGING

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1993 · $118,410

## Abstract

The main objective of aging research is to determine the fundamental
processes which explains maximal longevity and to understand the
underlying mechanisms of age-related disease processes in hope of
preventing debilities which affect the quality of life in old age.
Because of this objective, interest has been in the development of
biomarkers expedited by a pragmatic interest in establishing reproducible
scientific criteria for assessing the effectiveness of interventions that
affect aging especially in animal species that have life spans
significantly less than that of human.  Although many interventions have
been proposed, the only one which is currently scientifically valid in
altering aging is dietary restriction.

Pentosidine is a fluorescent protein cross-link isolated from senescent
human extracellular  matrix. It is formed through the nonenzymatic
reaction of pentose sugars such as ribose with lysine and arginine
residues.  A more recent study showed that hexoses (i.e., glucose) can
form this cross-link.  Pentosidine levels are responsive to metabolic
conditions which affect life span of humans and animals: a) it is
increased in hyperglycemia induced by diabetes, b) it is increased in
uremia which kills many rodent species, and c) it is decreased by dietary
restriction.

We propose to investigate the validity of pentosidine as a biomarker of
aging by testing the hypothesis that the rate of accumulation of
pentosidine is related to maximum life span of rodent species, and that
the genetic susceptibility to uremia will significantly increase, while
food restriction will decrease the accumulation rate, respectively.  A
long-term longitudinal study is proposed by measuring individual rates of
accumulation of pentosidine in skin and tail tendons of C57BL/6NNIA mice
and Fischer 344 rats fed ad libitum vs. food restricted from early life
(3 months) to spontaneous death of each animal.  Pentosidine will be
measured in tissue biopsies taken every 6 months and correlated with
maximum longevity of individual animals.  In a further study, pentosidine
will be measured cross-sectionally and longitudinally in skin and tail
tendons of Fischer 344 and F344/Brown-Norway F1 hydrid representing rat
species which are susceptible and resistant to renal disease,
respectively.

The further objective of this study is to determine the relationship of
pentosidine to another biomarker of aging, fluorophore "M", and to
investigate the molecular origin of pentosidine in vivo as reflected by
potential precursor sugars in the plasma of food restricted vs. ad
libitum fed rodents.

## Key facts

- **NIH application ID:** 3123071
- **Project number:** 1R01AG011080-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** DAVID R. SELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $118,410
- **Award type:** 1
- **Project period:** 1993-04-15 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123071

## Citation

> US National Institutes of Health, RePORTER application 3123071, PENTOSIDINE AS A BIOMARKER OF AGING (1R01AG011080-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123071. Licensed CC0.

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