IISER Mohali researchers uncovered an unexpected link between gut health and longevity, which could open new avenues for treating age-related diseases.
NOVEMBER 05, 2024 | BY RATNESHWAR THAKUR
What if the secret to living longer were connected to something as simple as how our bodies digest food? In the ever-evolving world of aging research, scientists are always trying to understand how our diet, genetics, and even drugs can stretch out our lifespans. Yet, the complex relationship between aging and our immune systems still holds many mysteries.
To tackle these mysteries, a research team led by Jogender Singh including Priyanka Das at Indian Institute of Science Education and Research, Mohali, in collaboration with Alejandro Aballay (Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, US), turned their focus to an enzyme known as calcineurin. This enzyme isn't unique to humans; it’s found in creatures ranging from yeast to roundworms. In humans, calcineurin has a well-documented role in the immune system, where it activates certain proteins that help fight off infections. However, these immune proteins are absent in Caenorhabditis elegans (or C. elegans), a microscopic roundworm. Despite lacking these proteins, C. elegans becomes an intriguing subject for research because scientists have discovered that blocking calcineurin extends the worm's lifespan. This curious observation inspired Das et al. to investigate further: How exactly does calcineurin affect the immune system and aging in C. elegans?
The Surprising Role of Calcineurin
The team’s experiments revealed a fascinating trade-off. Worms genetically engineered to lack calcineurin lived longer than their non-modified counterparts. However, when these long-lived worms were exposed to harmful bacteria, they fared much worse in fighting off the infection. A deeper look provided the explanation: calcineurin played a pivotal role in the worms’ ability to regulate their defecation cycle. Without calcineurin, the worms suffered from constipation and gut bloating, which had two major effects.
First, the bloating hindered the worms’ ability to clear bacteria from their digestive system, leaving them vulnerable to infections. But, interestingly, the same intestinal bloating activated cellular pathways typically associated with calorie restriction—a known strategy for promoting longevity across a wide variety of species. Essentially, the worms’ bodies reacted to the bloating by initiating survival mechanisms that extended their lifespan.
The Paradox of Longevity and Immunity
Das et al.'s findings illustrate an intriguing paradox: while inhibiting calcineurin can make C. elegans live longer, it also compromises their ability to fend off infections. This research adds to a growing understanding of how closely linked our gut health is to overall longevity. It also aligns with recent studies suggesting that gut bloating can influence a host of physiological traits, from how organisms seek food to how robust their immune responses are.
Broader Implications for Human Health
You might be wondering how gut health and an enzyme in worms relate to humans. The answer lies in calcineurin inhibitors like cyclosporine and tacrolimus, drugs used in human medicine to suppress the immune system and prevent organ rejection after transplants. Interestingly, one common side effect of these drugs is gastrointestinal bloating. Das et al.'s research suggests that the role of calcineurin in regulating gut health could extend beyond worms and might even be relevant for understanding side effects in humans.
Moreover, if bloating-induced pathways can extend lifespan in worms, could there be therapeutic potential for humans? This line of inquiry could lead to new approaches for tackling age-related diseases such as cancer, diabetes, or obesity. While there’s much more to learn, the idea that gut bloating or digestion rhythms could have such profound effects on longevity opens up an exciting area of future research.
Das and colleagues have shown that even the simplest creatures can teach us powerful lessons about our own health. It’s a vivid reminder that in the microscopic world of worms, there may be clues to healthier and potentially longer lives for us all.
"In longevity research, we almost always find that increased life span is associated with an improved health span, with elevated stress tolerance. This study is a rare example where life span benefits are decoupled from health span, showing that in future, longevity pills may not be one-size-fits-all drugs but may need to be personalized to cater diverse genotypes," commented Dr. Arnab Mukhopadhyay from National Institute of Immunology (NII), New Delhi, who is not associated with this study.
The study was supported by Department of Biotechnology, Ministry of Science and Technology, India, Ministry of Education, India, Council of Scientific and Industrial Research (CSIR), India and Science and Engineering Research Board, Govt. of India. The study has been published in the eLife journal.
Journal Reference:
Calcineurin inhibition enhances Caenorhabditis elegans lifespan by defecation defects-mediated calorie restriction and nuclear hormone signaling
Disclaimer:
SciSoup claims no competing interest. To ensure accuracy and scientific relevance, this science blog has been reviewed by the research team involved in the study.
