Millions of people worldwide suffer from metabolic diseases like obesity and type 2 diabetes, which pose serious health and economic challenges. These conditions are characterized by the body's diminished ability to adapt to changes in nutrient availability, especially during times of calorie restriction or nutrient stress.

In our recent study, we discovered that natural killer (NK) cells—an essential type of immune cell found in visceral fat tissue—play a pivotal role in the body's adaptation to energy shortages. Using advanced genomic techniques and experiments in mice and cell systems, we identified specific genomic regions associated with human accelerated regions (HARs; rapidly evolving elements) and linked to DNA repair mechanisms in NK cells.

During periods of caloric restriction, these HAR-linked genomic hubs become highly active. They coordinate the expression of genes involved in repairing DNA and responding to oxidative stress, which enhances the NK cells' ability to combat damaged cells and reduce inflammation. This activity leads to decreased DNA damage, less tissue scarring (fibrosis), reduced cell aging (senescence), and improved metabolic function.

We also pinpointed key factors that boost these adaptive responses, including certain proteins and signaling pathways that enhance NK cell function. By engineering NK cells with these beneficial factors and introducing them into mice with metabolic disorders, we observed significant improvements in metabolism, reduced inflammation, and long-term resilience against these diseases.

Our findings are significant because they reveal how enhancing the natural adaptability of NK cells can lead to better health outcomes. This research bridges the gap between genomics, metabolism, and evolution, offering new insights into how the body's own cells can be harnessed to develop innovative therapies for chronic conditions like obesity, diabetes, and aging-related diseases.

By identifying these principles, we enhance the bioengineering of cell therapy memory, enabling us to program cells with improved longevity and function. This understanding is also vital for computing natural intelligence, as it reveals how cells process information, adapt to stressors, and retain memory of past experiences to respond more effectively in the future. By deciphering the cellular mechanisms of adaptation and memory, we can develop smarter therapeutic strategies and inspire new approaches in artificial intelligence that mimic these natural adaptive processes.