Tissues in the body are supported by distinct stem cell populations that reside within structures of supporting helper cells known as stem cell niches. The primary purpose of stem cells is to deliver a supply of daughter somatic cells to replace lost cells, though they also provide signaling that affects cell behavior. All tissues undergo a slow turnover of cells as there is a limit to the number of times a somatic cell can replicate. Telomeres are lengths of repeated DNA sequences at the end of chromosomes that shorten with each cell division. When telomeres become too short, a cell reaches what is known as the Hayflick limit and either becomes senescent and is destroyed by the immune system or undergoes programmed cell death. Stem cells can maintain long telomeres via telomerase expression, and thus the replacement somatic cells created by stem cells also have long telomeres, beginning the countdown again.
In today’s open access paper, researchers look at the effects of fasting on a well-studied population of stem cells, those that support intestinal tissue. Intermittent fasting is well established to slow aging in animal studies, more so in short-lived species than in long-lived species. All of the reduced calorie intake strategies induce a beneficial response that improves metabolism and long-term health, provided sufficient nutrients are provided to stay well above the line of outright starvation. The function of stem cells is one of the many line items that are improved by these strategies. Normally, stem cell function declines with age for reasons that are complicated, incompletely mapped, and touch on many of the known underlying causes of aging. A lower calorie intake slows this process.
The process of aging is associated with a decline in cell, tissue, and organ function, leading to a range of health problems. Increasing evidence indicates that dietary restriction can counteract age-dependent effects and improve health and longevity in whole organisms, but less is known about the influence of aging and the impact of nutrition on individual organs of an organism.
In this study, we examined the intestine of the very short-lived aging model system, the African turquoise killifish (Nothobranchius furzeri), throughout its lifetime. We investigated the effects of age and nutrition on the preservation of gut tissue at stages corresponding to human neonatal, adolescent, adult, and old age, and integrated morphological measurements, histology, and transcriptomics.
The intestinal mucosa is characterized by folds and intervening interfold regions, where intestinal stem cells localize. The stem cells occur in clusters, and the cycle time of stem cells increases with age. We also observed a reduction in intestinal length and volume with age. Age-dependent transcriptomic profiling revealed significant changes in the expression of peripheral circadian clock genes and stem cell niche markers.
Notably, the majority of these genes maintained their adult gene expression levels in old age following intermittent fasting during adulthood. Therefore, our results demonstrate that the decline in structural intestinal tissue homeostasis is associated with a decline in stem cell activity that can be counteracted by intermittent fasting. Since the intestinal mucosa of killifish is similar to that of mammals, the results of this study can be translated to general gut biology.
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