In a groundbreaking study published in Nature Metabolism in 2025, researchers Ahrentløv, Kubrak, Lassen, and colleagues have unveiled new insights into the intimate relationship between dietary choices, gut-derived hormonal signals, and longevity. Their work centers on the protein-responsive gut hormone known as tachykinin, revealing its vital role in guiding food selection and, intriguingly, its lasting impact on lifespan. This discovery adds profound depth to our understanding of how the gut-brain axis modulates complex behaviors such as feeding and how these physiological pathways ultimately influence aging processes.
The study tackles a fundamental question in biology and nutrition: how does the body adjust its dietary preferences in response to nutritional needs, particularly protein intake? Proteins are indispensable macronutrients essential for a myriad of cellular functions, including repair, enzymatic activity, and immune responses. Despite their importance, the mechanisms by which the gut senses dietary protein and communicates this information to the brain to guide eating behavior have remained elusive. Here, tachykinin emerges as a key molecular signal that translates protein availability in the gut into specific feeding decisions, thus aligning dietary intake with the organism’s metabolic demands.
Tachykinins are a family of neuropeptides known for diverse physiological roles, including modulation of pain, inflammation, and neuroendocrine regulation. In this study, the focus is on a gut-derived tachykinin, which acts as a protein sensor. Upon detection of dietary protein, enteroendocrine cells in the gastrointestinal tract release tachykinin, which then signals to neural circuits influencing food preference. This gut-to-brain communication is not merely a reflexive response but appears to fine-tune an organism’s feeding repertoire, favoring protein-rich foods when protein is scarce and adjusting intake accordingly.
What makes this finding particularly compelling is the demonstration that modulation of tachykinin signaling has profound implications for lifespan. By experimentally manipulating this hormone’s pathway, the researchers observed significant alterations in the longevity of the model organisms studied. This suggests a link between nutrient sensing, diet choice, and the biological processes that regulate aging. Understanding these connections opens promising avenues for dietary interventions that may promote healthier aging by leveraging gut hormone pathways to optimize nutrition.
The experimental design involved cutting-edge genetic and biochemical approaches. Using genetically engineered models with specific disruptions or enhancements in tachykinin signaling, the team could assess the hormone’s impact on feeding patterns and longevity markers. Behavioral assays showed that animals with impaired tachykinin signaling displayed dysfunctional protein appetite, often neglecting protein-rich foods despite their critical need. Conversely, animals with heightened tachykinin activity demonstrated increased protein preference and subsequently altered metabolic profiles associated with improved survival metrics.
Importantly, this research underscores the critical role of the gut as a sensory organ beyond its traditional digestive function. The enteroendocrine system acts as an extensive nutrient sensor, and hormones like tachykinin serve as molecular messengers coupling dietary inputs to the central nervous system’s regulatory circuits. This hormonal signaling nexus plays a decisive role in balancing nutrient intake with physiological requirements, a process now shown to extend its influence to lifespan regulation.
Moreover, the connection between diet, gut hormones, and longevity emphasizes the evolutionary advantage of adaptive feeding behaviors. Organisms must navigate fluctuating food environments and prioritize nutrient acquisition for survival and reproduction. By harnessing protein-responsive gut signals, the body ensures precise nutrient homeostasis, optimizing resource allocation for maintenance and repair mechanisms that sustain health over time.
The researchers also explored the molecular pathways downstream of tachykinin reception, identifying several candidate receptors and intracellular signaling components implicated in the modulation of food preference circuits. These findings provide a mechanistic framework linking gut hormone action to neural substrates of decision-making. They also raise exciting questions about possible crosstalk between tachykinin signaling and other metabolic regulators, such as insulin and leptin, which jointly orchestrate energy balance.
From a translational perspective, this work holds potential relevance for human health and nutrition. Maladaptive feeding behaviors and protein malnutrition contribute to numerous age-related diseases and frailty. Enhancing or mimicking tachykinin signaling might serve as a therapeutic strategy to correct dietary imbalances, promote adequate protein consumption, and possibly extend healthspan. However, the authors caution that future studies are needed to explore the safety, efficacy, and feasibility of such interventions in human populations.
Furthermore, these findings add a novel layer to the study of diet-induced longevity pathways, traditionally focused on calorie restriction and macronutrient ratios. By identifying a specific hormone signaling system that drives protein appetite and influences lifespan, this research opens new windows into how dietary composition—not just calorie content—modifies aging trajectories. This nuanced understanding could revolutionize personalized nutrition approaches tailored to individual metabolic and hormonal profiles.
The study also presents compelling evidence that the gut-brain axis functions as a highly dynamic regulatory hub. It integrates environmental nutritional cues, internal energy states, and hormonal messaging to effect complex behavioral outputs, such as food selection. Tachykinin’s role as a key mediator within this network reveals a molecular basis for the intricate feedback loops that maintain metabolic homeostasis, thereby preventing nutrient deficiencies and promoting longevity.
Notably, the intricate relationship unveiled between tachykinin, dietary protein, and lifespan underscores the importance of interdisciplinary research, spanning neurobiology, endocrinology, metabolism, and aging science. It further exemplifies how integrative approaches are vital for elucidating the complex biological systems underlying health and disease. The use of advanced genetic techniques and rigorous behavioral analyses stands as a model for future studies aiming to decode physiological communication between organs.
Lastly, this work encourages renewed investigation into the diversity of gut hormones and their collective roles in orchestrating feeding behavior and metabolic health. Tachykinin joins a growing list of candidate molecules fundamental to the gut’s regulatory landscape. Elucidating how these factors interact and converge to shape dietary choices and aging outcomes remains a frontier of immense scientific and clinical interest.
Taken together, the research by Ahrentløv and colleagues marks a significant leap forward in understanding the molecular underpinnings of nutrient sensing, preference, and aging. It provides a striking example of how gut-derived signals exert systemic effects, linking dietary protein detection to behavioral and physiological pathways that impact lifespan. As science continues to unravel the complexities of the gut-brain connection, such findings will pave the way toward innovative strategies to improve human health and longevity through targeted modulation of gut hormones.
Subject of Research: Protein-responsive gut hormone tachykinin’s role in directing food choice and lifespan regulation.
Article Title: Protein-responsive gut hormone tachykinin directs food choice and impacts lifespan.
Article References:
Ahrentløv, N., Kubrak, O., Lassen, M. et al. Protein-responsive gut hormone tachykinin directs food choice and impacts lifespan.
Nat Metab (2025). https://doi.org/10.1038/s42255-025-01267-0
Image Credits: AI Generated
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