As we enter the new year, many people create New Year’s resolutions to improve their health.  This often includes the eternal promise to eat healthier and cut back on calories to lose weight.  However, recent research has shown that overall health, including weight loss, is actually not due to the “calories in-calories out” formula as we have been told over the years.  It is way more complicated than that.  Understanding the whole picture requires a deeper understanding of physiology. 

Throughout the coming year, I hope to share some of these developing insights in our rapidly changing understanding of the physiological mechanisms of health.

It is becoming more clear that chronic inflammation in the body can cause different types of health problems.  While acute inflammation is a body defense mechanism that uses the immune system to remove damaged cells, irritants, and pathogens and to initiate healing, problems begin when this acute inflammation becomes chronic.  Chronic inflammation has been shown to be the root cause of premature aging, cancer, autoimmune disorders, heart disease, diabetes, asthma, and neurodegeneration.

One of the main causes of chronic inflammation is irritation in the GI tract that, in addition to the health issues listed above, can lead to leaky gut, malabsorption of nutrients, and irritable bowel syndrome. It is also becoming more clear that different types of mental and emotional disorders, such as anxiety and schizophrenia, and various types of neurodegeneration, such as Alzheimer’s disease and Parkinson’s disease, may begin from the gut via the gut-brain axis.

One way we can get a handle on GI irritation is by using dietary interventions that are gaining more popularity, such as caloric restriction and various types of fasting, including 2-6 day fasts, intermittent fasting, fasting mimicking diets, and time restricted feeding.  

Today I want to focus on a recent study in PLOS Genetics that examines the effects of dietary restriction on improving lifespan, and especially healthspan.  The intestinal lining forms a permeable barrier that separates the body’s internal and external environments.  It allows the absorption of nutrients, but also keeps toxic substances and pathogens from entering the body. The intestines also regulates the interaction between the GI tract and the gut microbiome. 

Several mechanisms have been postulated to influence intestinal permeability. These include changes in the gut microbiota, secretion of mucus and anti-microbial peptides, tight junction proteins that prevent the cells in the gut wall from separating, and proper intestinal cell turnover. 

The study in PLOS Genetics examined proper intestinal turnover.   All cells in the body need to be replaced when they become aged or malfunctioning, via a process of programmed cell death called apoptosis, with new cells being produced by stem cells.  This is true in the gut where the turnover of cells is quite rapid.  The process of cell turnover needs to be tightly regulated or else problems can occur.  Cancer can begin if the cells are produced in too high a quantity and poor cell function can occur if the cells removed by apoptosis are replaced inadequately.  This tight regulation of intestinal cell turnover, which prevents an increase in intestinal permeability, declines as we age.

Results showed that dietary restriction slows the age-related decline in intestinal integrity by preventing excessive cell death that would lead to increased gut permeability and shortened lifespan. So how much do you need to reduce caloric intake to prevent age-related decline of gut function and lifespan?  While the exact answer is unknown,  research by Valter Longo, PhD suggests that at least 20%  and perhaps up to 40% of caloric restriction is needed.  While regularly cutting back calories 20-40% may be a good strategy to improve healthspan, and weight loss, it can be difficult for many people to maintain.  Could fasting-type interventions help as well?  Recent research suggests yes and these topics will be the subject of upcoming posts.

Dietary restriction improves intestinal cellular fitness to enhance gut barrier function and lifespan in D. melanogaster.  Akagi et al. November 1, 2018

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007777