Impact of circadian-microbiome interaction on the GUT-pancreas axis in aging
Active Cooperative Agreement Awarded Last action
- Award ID
- U01AG086145
- Recipient
-
University Of Texas Health Science Center At Houston UEI ZUFBNVZ587D4 Part of University Of Texas System
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,936,264
Award facts
- Assistance listing
- 93.866 Aging Research
- Completion date 47% complete
- Place of performance
- Houston, TX 77030, USA
Award details come from USAspending.gov.
Description
- Abstract
- Low grade systemic inflammation (or inflammaging) associates with many age-associated diseases. Among the mechanisms that incite inflammaging, damage to the intestinal barrier is likely among the most important. As a common feature of aging, several studies have indicated a close connection between intestinal barrier dysfunction, changes in the GUT microbiota and chronic inflammation along with systemic multi-organ injuries. One such organ is the pancreas where barrier impairment is known to contribute to several age- associated disorders, including impaired insulin secretion and cancer. Despite these connections, why the intestinal barrier becomes dysfunctional as we age, what drives the changes in microbiome with aging and how these factors affect the quality of aging are unknown. Answers to these questions will help US identify mechanisms of healthy aging which is a critical knowledge gain towards increasing quality of life in our aging population. Studies from our group suggest that both the intestinal barrier and microbiome can change in response to exposure to lifestyle factors (e.g., diet, eating time), that are important modifiable determinant of healthy aging. In fact, changes in our lifestyle are likely why "aging"-related pathologies are on the rise. Of the several lifestyle factors that may affect aging, disruption of circadian rhythms that govern a wide spectrum of host physiology is quite common in our modern society. We and others have shown that disruptions of circadian rhythms negatively affect intestinal microbiota and barrier function, leading to intestinal and extra-intestinal injuries including in pancreas. Here we will study the impact of circadian disruptions on the GUT-pancreas axis in aging through microbial signaling. In aim 1, we will study how food timing (as a proxy for peripheral circadian disruption) affects intestinal driven inflammation and pancreas aging in mice. We will determine novel microbiome-host rhythms that are under circadian cues and are connected to the GUT-pancreas aging processes. Human studies in aim 2 will aid in establishing the causal role of microbial signaling in mediating the effect of the host circadian disruption on the GUT-pancreas physiology. Our work will provide critical insights into targetable GUT-centric anti-aging mechanisms that could be considered for future trials as well as for developing prophylactic therapies.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $639,628 | |
| Amendment | $0 | |
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| Amendment | $640,435 | |
| Amendment | $640,435 | |
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| Amendment | $0 | |
| Amendment | $671,922 | |
| Amendment | $671,922 | |
| Original award | $671,922 |
Show all 12
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Rush University Medical Center | $124,685 | |
| Northwestern University | $591,590 |
Quick answers
Who received award U01AG086145?
U01AG086145 was awarded to University Of Texas Health Science Center At Houston by National Institute on Aging (National Institutes of Health) on August 1, 2024.
How much is award U01AG086145 worth?
$3,936,264 has been obligated on U01AG086145.
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