# Post-Transcriptional Control of Aging-Associated Inflammation and Bone Homeostasis

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $378,813

## Abstract

ABSTRACT
With advancing age, the immune system undergoes dynamic changes characterized by both impairment of
adaptive immunity and activation of low-grade chronic inflammation. This chronic activation of inflammation
associated with aging or `inflammaging'. Tristetraprolin (TTP) is an RNA binding proteins that post-translationally
bind to adenylate-uridylate–rich elements in the 3′-UTR of target mRNAs (including key pro-inflammatory mRNAs
e.g. TNFα, COX-2 and IL-6) to promote their rapid turnover. Importantly, we have recently demonstrated that
failure to regulate expression of cytokines at the posttranscriptional level contributes to chronic inflammation and
spontaneous alveolar bone loss with age in TTP-/- mice compared to age/sex match controls. Thus, TTP
expression appears to be essential for alveolar bone homeostasis in an age-dependent manner. Our preliminary
data in this application and recently published data strongly support the concept that macrophages and myeloid-
derived suppressor cell (MDSC) populations are expanded with age in TTP-/- mice, with concomitant reduction
in lymphocyte populations. Taken together, our results support that notion that TTP may be a critical intrinsic
factor of inflammaging and myeloid lineage expansion/differentiation that contributes towards skeletal
homeostasis. We propose to test the hypothesis that TTP controls inflammaging and impacts alveolar bone and
long bone skeletal health with age. The specific aims of the proposal are: 1) define the role of myeloid-derived
TTP on bone homeostasis with age; 2) determine the mechanisms that TTP uses to alter osteoclastogenesis
with age; and 3) Establish if increased TTP expression alters bone remodeling during healthy aging. At the
conclusion of these studies, new insights regarding TTP will be provided for future studies where would be
potentially a therapeutic target for healthy aging of the oral and non-oral skeletal tissues.

## Key facts

- **NIH application ID:** 10155463
- **Project number:** 5R01DE028258-04
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Keith L Kirkwood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,813
- **Award type:** 5
- **Project period:** 2018-09-07 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155463

## Citation

> US National Institutes of Health, RePORTER application 10155463, Post-Transcriptional Control of Aging-Associated Inflammation and Bone Homeostasis (5R01DE028258-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10155463. Licensed CC0.

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