Researchers have taken a look at how caloric restriction seems to improve intestinal stem cell function in a new open-access study.
Inflammaging is a precursor of age-related diseases
The lining of the intestines helps to prevent the entry of microbes and unwanted molecules into the bloodstream beyond; however, as we age, the integrity of this barrier declines, causing microbial burden to rise and, with it, chronic inflammation.
This chronic age-related inflammation, often referred to as inflammaging, has multiple sources, including loss of intestinal barrier integrity and a resulting rise in microbial burden, senescent cells, cell debris, and immunosenescence. Some researchers even suggest that microbial burden resulting from the loss of intestinal barrier integrity could potentially be the origin point of inflammaging, the initial spark that sets the powder keg alight.
Inflammaging precedes a variety of age-related diseases, including atherosclerosis, arthritis, hypertension, and cancer [1-3]. Inflammaging presents a persistent background of inflammation that also leads to increasingly poor tissue repair and regeneration as we age .
As we age, the stem cells in our tissues and organs, which provide us with a steady supply of fresh cells, begin to slow down, and that flow of replacement cells begins to falter.
This decline of stem cell activity is known as stem cell exhaustion, and it is one of the proposed reasons we age. Stem cells become increasingly inactive as we age for various reasons, including damage and the chronic inflammation of inflammaging, which alters the signaling environment and suppresses their ability to function.
Caloric restriction appears to support intestinal stem cells
The researchers of a new study have shown how caloric restriction appears to be beneficial to the function of stem cells that reside in the tissues of the intestine . Caloric restriction is the practice of consuming fewer calories while still consuming an optimal amount of nutrition. The key is to reduce calorie intake while avoiding malnourishment.
Caloric restriction can reduce calorie intake by up to 40% less than normal, though 20-25% is typical. It has been shown to increase healthy lifespan in multiple species across many published studies.
The data in this study suggests that the decline of intestinal stem cell activity is slowed down through caloric restriction. The researchers also examined how caloric restriction limits the mutation rate of stem cells and how it lowers the retention of mutated cells in the intestinal tissue.
Calorie restriction (CR) extends lifespan through several intracellular mechanisms, including increased DNA repair, leading to fewer DNA mutations that cause age-related pathologies. However, it remains unknown how CR acts on mutation retention at the tissue level. Here, we use Cre-mediated DNA recombination of the confetti reporter as a proxy for neutral mutations and follow these mutations by intravital microscopy to identify how CR affects retention of mutations in the intestine. We find that CR leads to increased numbers of functional Lgr5+ stem cells that compete for niche occupancy, resulting in slower but stronger stem cell competition. Consequently, stem cells carrying neutral or Apc mutations encounter more wild-type competitors, thus increasing the chance that they get displaced from the niche to get lost over time. Thus, our data show that CR not only affects the acquisition of mutations but also leads to lower retention of mutations in the intestine.
This study offers yet more evidence that caloric restriction can be potentially beneficial in the context of aging and health. It should be noted that anyone who practices caloric restriction should make a great effort to continue consuming adequate nutrition while doing so.
 Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med (2010) 16(5):238–46. doi: 10.1016/j.molmed.2010.03.003
 Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R. M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017). Senescent cells: an emerging target for diseases of ageing. Nature Reviews Drug Discovery, 16(10), 718.
 He, S., & Sharpless, N. E. (2017). Senescence in health and disease. Cell, 169(6), 1000-1011.
 Straub, R. H., & Schradin, C. (2016). Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs. Evolution, medicine, and public health, 2016(1), 37-51.
 Bruens, L., Ellenbroek, S. I. J., Suijkerbuijk, S. J. E., Azkanaz, M., Hale, A. J., Toonen, P., … & van Rheenen, J. (2020). Calorie Restriction Increases the Number of Competing Stem Cells and Decreases Mutation Retention in the Intestine. Cell Reports, 32(3), 107937.