Table of Contents
- 1 Brain Health and Longevity
- 2 Key Findings from the University of Washington Study
- 3 Exploring the Brain-Adipose Tissue Communication Pathway
- 4 The Role of Ppp1r17 Protein and Fight-or-Flight Response
- 5 Age-Related Decline in the Feedback Loop and Its Consequences
- 6 Research Implications and Future Interventions
- 7 Final Thoughts
This article explores a University of Washington study that links the activation of certain hypothalamic brain cells to increased longevity. Highlighting a unique interaction between the brain and adipose tissue, the research offers new insights into the aging process.
Brain Health and Longevity
Longevity increases when specific brain cells in the hypothalamus are activated. This demonstration by a team of biologists from the University of Washington is a reminder of the importance of brain health for longevity. But this research goes further. It reveals in the journal Cell Metabolism that these brain cells communicate with adipose tissue to produce cellular fuel and thus counteract certain effects of aging.
Key Findings from the University of Washington Study
The study suggests that the communication pathways between different organs in the body also regulate aging. It is clear that when these lines of communication are open, the body’s different organs and systems work better together. As we age, these lines of communication deteriorate and organs become less able to receive the molecular and electrical messages they need to function.
Exploring the Brain-Adipose Tissue Communication Pathway
The study analyzed these communication pathways crucial to the healthy aging of mice, and one communication pathway linking the brain to the body’s fat tissue caught the researchers’ attention: this pathway is set up as a feedback loop that appears to be central to energy production throughout the body. The research suggests that this specific set of neurons in the brain’s hypothalamus, when active, sends signals to the body’s adipose tissue to release energy. These neurons, located in the dorsomedial hypothalamus (DMH), produce Ppp1r17. When this protein is present in the nucleus, the neurons are active and stimulate the sympathetic nervous system, which regulates the body’s fight or flight response.
The Role of Ppp1r17 Protein and Fight-or-Flight Response
The fight-or-flight response is known to have far-reaching effects throughout the body, including increased heart rate and slower digestion. As part of this response, neurons in the hypothalamus trigger a chain of events that activate neurons that regulate the white adipose tissue stored under the skin and in the abdominal region. Activated adipose tissue releases fatty acids into the bloodstream, which can be used as fuel for physical activity. And also releases another important protein, an enzyme called extracellular nicotinamide phosphoribosyltransferase (eNAMPT), which feeds back to the hypothalamus and allows the brain to also produce fuel to function.
Age-Related Decline in the Feedback Loop and Its Consequences
This feedback loop, which is essential for the body and brain to be fed and function, slows down over time. With age, the Ppp1r17 protein tends to leave the nucleus of the neurons and, when this happens, the neurons of the hypothalamus send weaker signals. The deterioration of this circuit with age thus contributes to the increase in chronic health problems typical of natural aging.
When this circuit is kept artificially open and active in mice, even the oldest mice remain physically active, age more slowly, and live longer. In practice, the mice in which the researchers kept the brain fat feedback circuit active lived 60 to 70 days longer than the control mice which corresponds to an increase in lifespan of around 7%. In humans, this 7% increase in a 75-year lifespan would equate to an extra 5 years of life.
Research Implications and Future Interventions
These observations suggest future interventions aimed at maintaining the feedback loop for longer to slow down the effects of aging.
“It is therefore possible, through the manipulation of certain brain cells, to delay aging and extend healthy lifespan, here in mice,” summarizes lead author Dr. Shin-ichiro Imai, Professor Emeritus of Developmental Biology at the University of Washington. “Demonstrating this effect in a mammal is an important step in aging research.”
“We can imagine a possible anti-aging therapy that involves administering eNAMPT in different ways. We have already shown that administering eNAMPT via extracellular vesicles increases cellular energy levels in the hypothalamus and extends the lifespan of mice.”
The study’s innovative approaches, including DMH-specific Prkg1 knockdown and chemogenetic activation of DMHPpp1r17 neurons, demonstrate a novel pathway to potentially slow aging. While these methods are currently experimental in mice, their future adaptation for human use could mark a significant leap in anti-aging treatments, offering hope for enhanced health and longevity in our later years.
Tokizane, K., Brace, C. S., & Imai, S. (2023). DMHPpp1r17 neurons regulate aging and lifespan in mice through hypothalamic-adipose inter-tissue communication. Cell Metabolism. https://doi.org/10.1016/j.cmet.2023.12.011