# Kynurenine: a potential link between age-related decreases in bone mass and kidney function

> **NIH VA IK2** · CHARLIE NORWOOD VA MEDICAL CENTER · 2020 · —

## Abstract

Project Summary
Osteoporosis is a major public health problem affecting 44 million Americans and costing an estimated $17 billion
in 2001. Bone fractures in the elderly in particular can result in significant morbidity and mortality. Understanding
the renal mechanisms that underlie bone loss in aging is the focus of this application. The kidney is responsible
for Vitamin D synthesis and contributes to the control of calcium and phosphate levels. Bone-produced FGF23
and its co-receptor, Klotho help to regulate these processes, and dysregulation in these factors or any of their
downstream signals can lead to bone loss. Aging also impairs kidney function which may also contribute to
aging-related bone loss. However, whether the bone can affect kidney function is not known.
Tryptophan, one of nine essential amino acids, is a potent anti-oxidant but its levels decrease with aging;
however, its stable oxidized metabolite, kynurenine increases with age and inhibits bone marrow stem cell
proliferation. Work from our laboratory has shown that kynurenine feeding in mice results in bone loss. Our
central hypothesis is that augmented kynurenine levels induce an aged phenotype resulting in both bone loss
and kidney dysfunction through the FGF23/αKlotho pathway.
Dr. Irsik will conduct these experiments under the mentorship of Dr. Wendy Bollag, who has expertise in signal
transduction and has been continuously VA Merit-funded for a dozen years. In order to gain knowledge in aging
research, she will work towards a certificate in gerontology and collaborate with the members of her career
advisory committee to gain expertise in experimental design in aging studies. Dr. Isales will provide expertise in
aging and bone research while Dr. Carbone is an expert in bone issues in veterans and Dr. Dong is recognized
for his research in acute kidney injury. Dr. Irsik will expand her current research skills by learning to perform
DXA, CT and bone histology through the collaborative efforts of Drs, Bollag and Isales. Dr. Dong will provide
assistance in her renal studies, and Dr. Carbone will teach her how to work with large datasets available through
the VA. She will interact weekly with all the members of the Bone Group, comprised of both clinicians and basic
scientists from multiple departments and disciplines, presenting her own research twice a year. She will present
her research at a minimum of two international meetings per year (ASBMR, ASN, GSA or Experimental Biology).
Her transition to independence will be enhanced by the mentorship of Dr. Bollag, who has guided many trainees
to successful careers in academic research. She provides the perspective of a successful woman PhD scientist
while Dr. Isales is a clinician who has advocated for under-represented minority researchers for many years.
Together these two investigators, who have a successful track record of collaborating for approximately 30 years,
will help to ensure that Dr. Irsik receives the mentoring neces...

## Key facts

- **NIH application ID:** 10016787
- **Project number:** 1IK2BX004997-01A1
- **Recipient organization:** CHARLIE NORWOOD VA MEDICAL CENTER
- **Principal Investigator:** Debra Irsik
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016787

## Citation

> US National Institutes of Health, RePORTER application 10016787, Kynurenine: a potential link between age-related decreases in bone mass and kidney function (1IK2BX004997-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10016787. Licensed CC0.

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