Chapter 179
Changing Aging — 16
While caloric restriction has improved lifespan in rodents, the impact in nonhuman primates and people is less clear. Recall the contradictory evidence in the two large monkey studies with an over twenty-year follow-up, one by the University of Wisconsin and the other by the National Institute on Aging. The Wisconsin study was more restrictive of calories, with one meal a day and a sixteen-hour fasting period; the National Institute on Aging protocol left food out overnight for ad lib intake. While lifespan was only extended in the Wisconsin study, both showed improvement in health span—age-related diseases of diabetes, cardiovascular disease, and osteoarthritis.
Figure 12.6. Healthy lifestyle factors and gain in life years, by men and women. Adapted from Ryoto Sakaniwa et al., “Impact of modifiable healthy lifestyle adoption on lifetime gain from middle to older age,” Age and Ageing 51, no. 5 (May 1, 2022), https://doi.org/10.1093/ageing/afac080.
In the section on nutrient sensing, I mentioned the two studies that suggested mild caloric restriction (12–14%) was associated with reduced biological aging. A subsequent report from one of these studies provided a new dimension of caloric restriction’s benefit—the immune system. Specifically, the thymus gland, which in adolescence diminishes in its ability to produce T cells and accumulates fat, was restored. Fat tissue was remodeled, and a reduction of a platelet-activating factor (PLA2G7) expression in that tissue was correlated with reduction of body-wide inflammation. The removal of that gene in mice provided evidence for blunting inflammation and preserving thymus function in old mice.
The various time-restricted eating and intermittent fasting practices discussed in chapter 3 have not provided support for antiaging impact but have shown improvement in the immune response. Along with caloric restriction, they are associated with favorable changes in the gut microbiome composition and better anticancer effects in experimental models. There has also been interest in a fasting-mimicking diet, a five-day intake of a plant-based, low-calorie, low-protein diet every four weeks, which showed beneficial effects in mice and was tested in a randomized trial of one hundred people (mean age forty-three years, BMI 27). Three five-day cycles of this diet led to better insulin sensitivity, less liver fat, an increase in lymphocytes to white blood cell ratio (a favorable immune system age metric), and a decrease of 2.5 years in biological age. The biological age metric was not based on DNA methylation but instead used a group of biomarkers. Valter Longo and Rozalyn Anderson, researchers based at the University of Southern California, have long been advocates of the fast-mimicking diet; in a review, they described the “longevity diet” for extended lifespan and health span as “characterized by a mid to high carbohydrate and low but sufficient protein intake that is mostly plant based but includes regular consumption of pesco-vegetarian-derived proteins.”