Devising a new dialogue for nutrition science: how life course perspective, U-shaped thinking, whole organism thinking, and language precision contribute to our understanding of biological heterogeneity and forge a fresh advance toward precision medicine

Abstract

The process of designing and implementing individualized health-promoting interventions, nutritional or otherwise, is fraught with great difficulty owing to the heterogeneity inherent in factors that influence healthy longevity. This article proposes that careful attention to three principles-life course perspective, U-shaped thinking, and whole organism thinking-creates an attitudinal framework that can be used to reframe biological heterogeneity into the clinically relevant question: Who will benefit? The search for tools to cope with the complexity of this heterogeneity has been dominated by technological advances, including state-of-the-art "-omics" approaches and machine-based handling of "big data." Here, it is proposed that language precision and nuanced category usage could provide critical tools for coping with heterogeneity, thereby enabling interventionalists to design and implement strategies to promote healthy longevity with greater precision. The lack of a clear understanding of "Who will benefit?" stands as a major obstacle to the design and implementation of nutritional strategies to optimize healthy longevity. This article opens a new dialogue situating the principles of life course perspective, U-shaped thinking, and whole organism thinking, along with cultivating an attitude of language precision at the very core of accelerating creative discovery and refining practical advance in the field of nutrition science.

Keywords: aging; dose response; longevity; neologism; pet dogs; trade-offs.

Figure 1.

The biology of healthy longevity: principles and practice. Attention to three principles—life course perspective, U-shaped thinking, and whole organism thinking—creates an attitudinal framework that reframes biological heterogeneity into the clinically relevant question: Who will benefit? Language precision and nuanced category usage provide critical tools for coping with heterogeneity enabling interventionalists to design and implement nutritional strategies with greater precision.

Figure 2.

(A) Finding the optimal dose for disease risk reduction. A hypothetical linear relationship is shown between the risk of a particular disease and the dose of a disease preventive agent, consistent with the notion that “more is better”. (B) Dose–response model adapted from Mertz (1981). The U-curve predicts that the biological response to an essential nutrient is characterized by an optimal middle range, consistent with the notion that “more is not necessarily better” (Waters et al., 2005; with permission).

Figure 3.

The dog U-curve. The dog U-curve was discovered by studying the dose–response relationship between selenium status and prostatic DNA damage in elderly dogs over a range of selenium concentration achievable in human populations (Waters et al., 2005) (with permission). Each data point represents the result from one dog.

Figure 4.

The dog U-curve: a map to interpret the disappointing results of the selenium and vitamin E cancer prevention trial (SELECT). (A) The dog U-curve predicts that the selenium status of the average man in SELECT prior to selenium supplementation (“You Are Here”) is already in the optimal range for minimizing prostate cancer. (B) The dog U-curve predicts that the selenium status of the average man in SELECT after selenium supplementation (“You Are Here”) clearly exceeds the optimal range for minimizing prostate cancer risk. Adapted from Waters and Chiang (2018).

Figure 5.

Categories are starting points for present practice and future inquiry (see text for explanation).

Figure 6.

The art of sufficient particularity: two important aspects of language precision. The practices of using neologism and avoiding naïve substitution are critical for developing the deeper discriminating power to deliver benefits as one navigates biological heterogeneity (see text for explanation).