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2.1 Host Nutrient Triage: The survival strategy our body uses to allocate nutrients during times of scarcity and why it may be harmful to long-term health

Bruce Ames, a prominent biochemist, proposed the Nutrient Triage Theory in 2006, suggesting that when the body is deficient in certain nutrients, it prioritizes them for essential functions, which can lead to the diversion of nutrients away from non-essential functions. This, in turn, can cause interrupted nutrient supply at the cellular, organelle, organ, system, and whole-organism levels, which can contribute to the development of degenerative processes and various chronic diseases.

During periods of an energy shortage, nutrient scarcity, or compelling physiologic demands, nutrient triage is regulated by integrated stress response (ISR) mediators, such as AMP-activated protein kinase (AMPK), which help coordinate the utilization and storage of limited energy and nutrients. At the cellular level, reserved nutrients prioritize the maintenance of critical functions, such as the generation of ATP, the preservation of cellular membrane integrity, the maintenance of DNA stability, and the regulation of apoptosis. At the organelle level, scarce nutrients are allocated to the most critical organelles, such as the mitochondria, ribosomes, lysosomes, and others, while downregulating less essential processes. For example, the body may maintain ATP generation in mitochondria, while downregulating protein synthesis in ribosomes. These allocations ensure the survival of the cell and the organism as a whole.

The triage processes are also evident at the organ level. Different organs may compete for limited nutrients. This nutrient allocation is regulated by hormones and other signaling molecules that coordinate the host stress responses. For example, the liver may prioritize the provision of glucose to the brain over other organs such as the muscle, which could switch to alternative fuels such as fatty acids. Similarly, the adrenal gland may prioritize the production of stress hormones, such as cortisol, over other functions, such as the synthesis of sex hormones. In addition to hormones, the autonomic nervous responses at the organ level also regulate the changes in blood flow, which redirects nutrients and oxygen to critical organs and away from less essential tissues during the nutrient shortage.

At the organism level, the allocation of limited nutrients prioritizes critical physiological functions that are essential for short-term survival such as maintaining heart function, preserving lean muscle mass, and supporting immune function over less critical processes such as growth, development, and reproduction. This nutrient triage is regulated by changes in hormone levels, gene expression, and other physiological responses that coordinate the response of the organism to stress. The temporary put-on-hold or slow-down of nutrient distribution ensures the body's survival in the short term while trading off long-term health.

In summary, the Nutrient Triage Theory provides a useful framework for understanding the complex relationships between nutrient deficiencies and chronic disease development such as obesity, diabetes, and cardiovascular disease. Addressing long-term nutrient imbalances through targeted interventions, including dietary modifications and nutritional intervention, may play an important role in the prevention and management of these modern-day illnesses.

Ames, B.N., Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proceedings of the National Academy of Sciences of the United States of America, 2006. 103(47): p. 17589-17594.

Ames, B.N., Musings in the twilight of my career. Free Radic Biol Med, 2022. 178: p. 219-225.

McCann, J.C. and B.N. Ames, Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging. Faseb j, 2011. 25(6): p. 1793-814.

Lee, M. and J. Shin, Triage of oxidation-prone proteins by Sqstm1/p62 within the mitochondria. Biochemical and Biophysical Research Communications, 2011. 413(1): p. 122-127.

McCann, J.C. and B.N. Ames, Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr, 2009. 90(4): p. 889-907.

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