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1.7. The host nutrient reserve: a critical modulator of Integrated Stress Response.

The host nutrient reserve plays a critical role in the Integrated Stress Response (ISR). The reserve encompasses the presence of macro- and micronutrients, while the metabolic reserve comprises the body's capability to metabolize these resources efficiently for both catabolism and anabolism. In times of ISR, the body quickly adapts to cellular stressors such as nutrient deprivation, oxidative stress, misfolded proteins, toxins, or infections, with the two reserves working in unison to enable an effective adaptive response.

For optimal stress response and recovery, the body requires balanced nutrient and metabolic reserves. For instance, during the event of an infection, the immune system is activated, heart rate and breathing increase, and nutrients and energy are channeled to the affected area to support responding activities. This process can only occur when adequate nutrients are available and the metabolic reserve can effectively utilize them. Conversely, insufficient reserves can impair the body's ability to defend and repair, making it susceptible to illness.

To sustain good health in the face of modern-day challenges, an adequate balance of macro- and micronutrient reserves is essential. Prolonged insufficient reserves trigger nutrient triage, which prioritizes short-term survival over long-term well-being. Such maladaptation contributes to the present-day prevalence of chronic metabolic illnesses.

Pakos-Zebrucka, K., et al., The integrated stress response. EMBO reports, 2016. 17(10): p. 1374-1395.

Bilen, M., et al., The integrated stress response as a key pathway downstream of mitochondrial dysfunction. Current Opinion in Physiology, 2022. 27: p. 100555.

Ames BN. Musings in the twilight of my career. Free Radic Biol Med. 2022 Jan;178:219-225. doi: 10.1016/j.freeradbiomed.2021.11.038. Epub 2021 Dec 1. PMID: 3486387

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