Slowing Down Inflamm-Aging with Diet

Source: istock

What if I tell you that you can greatly improve your immune system by just cutting your calories by 40%? 

If you are as skeptical as I, your cursor would be on its way to the “close tab” button after reading that first sentence. In my very personal and non-scientific opinion, a 40% caloric restriction (CR) essentially goes hand in hand with a 90% happiness reduction. Besides, the study that demonstrates the immune benefit of CR was done in a mouse model, so the benefit may not even be guaranteed in humans!

To investigate the benefits of CR in human immunity, Spadaro and colleagues conducted a human study. Specifically, the research team is interested in the effect of CR on inflamm-aging, the chronic low-level inflammation that develops with age. These chronic inflammations occur even in the absence of harmful pathogens and may damage one’s own organs.

A previous study has shown that the thymus, a critical organ for T cell development, is vulnerable to the aging process. The decreased thymic function over age was evident by the decline in T cell production and T cell diversity. This loss of thymic function has significant implications during infections because T cells are key players of adaptive immunity. 

For this reason, Spadaro and team were interested in assessing the effect of CR in the human thymus. However, 40% CR cannot be imposed without significantly affecting the participants’ quality of life. Therefore, the research team used a moderate 14% CR that has been previously shown to be feasible. Interestingly, the CR volunteers exhibited higher T cell production after 2 years of CR compared to their own baseline. This finding suggests that CR may counteract the age-related decline in T cells, thereby strengthening adaptive immunity against new infections. 

Moving onto the innate immune system, the adipose (fat) tissue is naturally another area of interest in a CR study, especially given its established role in regulating inflammation. When the researchers examined the adipose tissue transcriptome (mRNA profile), they observed significant changes in the gene expression of CR volunteers. These changes reflected decreased innate immune activation, which was consistent with the hypothesis that CR protects us against inflamm-aging. 

The researchers delve deeper into this protective effect of CR by examining the changes in the myeloid cells, the cellular components of innate immunity. The transcriptome analysis revealed that PLA2G7 (Phospholipase A2 Group VII) was strongly inhibited in the macrophages of CR patients. However, the function of PLA2G7 in macrophages was a mystery, at that time.

The research team then returned to the mouse model to investigate the function of PLA2G7. They create mice that are deficient in PLA2G7. Interestingly, these PLA2G7-deficient mice gained lesser weight and fat mass from a high-fat diet as compared to the wild-type (WT) control. Furthermore, the macrophages of PLA2G7-deficient mice showed lower proinflammatory factor expression. At 2 years old, the PLA2G7-deficient mice (which is equivalent to ~70 human years!) had better thymic function compared to their WT counterpart. 

Together, the research team confirmed the benefits of moderate CR in reducing self-damaging chronic inflammation. On the other hand, the findings suggested that CR strengthens the adaptive immunity against pathogens through improved thymic function. Their discovery of PLA2G7 deficiency as a mediator of these benefits may hopefully serve as a new therapeutic target in the future. 

Source:

Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, Nguyen K, Aladyeva E, Predeus AN, Smith SR, Ravussin E, Galban C, Artyomov MN, Dixit VD. Caloric restriction in humans reveals immunometabolic regulators of health span. Science. 2022 Feb 11;375(6581):671-677. doi: 10.1126/science.abg7292.

Article author: YongGuang Jiang. Yong is an IRTA postbaccalaureate fellow at the National Institute of Health. His research is focused on studying the role of plasmin and neutrophil elastase in hematopoietic recovery.

Editor: Sutonuka Bhar. Sutonuka is a PhD candidate at the University of Florida. Her work focuses on host immune responses against viruses and bacterial membrane vesicles.

Check out Antibuddies’ blog post “Slowing Down Inflamm-Aging with Diet”.

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