Intermittent fasting rejuvenates the immune system

In a supplemental issue of Current Developments in Nutrition (Vol. 9, Suppl 2, 2025), the authors report that intermittent fasting (IF) improves immunity during aging by redirecting myeloid cell development and reducing systemic inflammation. The work is published as a conference abstract NUTRITION 2025 (No. 106019).

Background

Why the interest in IG and immunity?
With age, chronic “silent” inflammation develops — inflammaging: low-level, sterile, supported by multiple stimuli (defective cellular debris, microbiota, excess nutrients). It is associated with the risk of diseases of aging and a weakened immune response. This is the basic framework, the adoption of which began with the work of Franceschi et al. and is regularly updated by modern reviews. =

What happens to hematopoiesis with aging?
Hematopoietic stem cells shift toward a “myeloid bias”: more descendants of the myeloid line (monocytes/macrophages, neutrophils), less of the lymphoid line. This “shift” is associated with a proinflammatory environment and clonal rearrangements characteristic of age.

The role of macrophages and autophagy.
Autophagy in macrophages is one of the key regulators of their polarization and function. Correct functioning of autophagy helps to switch off inflammation and promote the "resolution" of the inflammatory response; autophagy defects, on the contrary, support chronic inflammation and tissue damage. This is confirmed by both fundamental reviews and model studies.

Why intermittent fasting (IF)?
IF and related protocols (time-restricted eating, alternate-day fasting, fasting-mimicking diet) affect nutrient signaling pathways and subsequently activate autophagy, which is considered one of the main mechanisms of their systemic effect. In animal models and early clinical studies, IF/FMD reduced inflammatory markers, improved metabolism, and in some cases, rejuvenated immune signatures.

What is known in humans today?
Summary reviews and “umbrella” meta-analyses on IH indicate benefits for a range of health outcomes (weight, lipids, glycemia) and modest reductions in inflammatory markers (e.g., CRP, IL-6) in individual protocols/cohorts. However, heterogeneity across designs is high, and detailed immune phenotypes (e.g., myeloid reprogramming) have been limited—a gap that new studies aim to fill.

How does this fit with the new abstract?
The message that IG "reconfigures" the systemic myeloid lineage and reduces tissue inflammation through restoration of autophagy in macrophages logically fits with existing mechanistic data (autophagy ⇄ macrophage polarization) and clinical observations of a decrease in inflammatory markers in IG. The novelty is in the focus on the age-related immune system and the stated link "IG → autophagy in macrophages → anti-inflammatory shift in the myeloid pool."

Where do questions remain?
Precise IG regimens (window duration, intervention duration), reproducibility at different ages/sex, tolerability in concomitant diseases and, most importantly, the scale of clinically significant effect on immune outcomes - all this requires full-length, detailed publications and RCTs with immunophenotyping (single-cell transcriptomes, phagocyte functions, complement system, etc.).

What did they do?

The authors (Han et al., Texas A&M) studied the effects of IG on the immune system of an aging organism, focusing on the myeloid lineage (primarily macrophages) and markers of the "inflammatory background" (inflammaging). According to the abstract, IG regulates the differentiation of myeloid cells and their "reprogramming", which is accompanied by a decrease in systemic inflammation.

Mechanisms (according to the abstract)

The key observation is the activation of autophagy in macrophages against the background of IG. According to the authors, this “rescues” age-related autophagy and reduces pro-inflammatory activation of macrophages, which gives an anti-inflammatory effect at the level of tissues and the entire body.

Why is this important?

With age, immunity shifts toward a “myeloid bias,” and levels of chronic sterile inflammation increase, leading to a weaker response to vaccines and a higher risk of infections and diseases of aging. If IG does indeed shift the balance of innate immune function and reduce inflammation, it may provide a feasible, non-drug approach to supporting immune health in middle-aged and older adults. These findings are consistent with a growing body of work on the benefits of dietary restrictions and “fasting-mimicking diets,” which have shown reductions in inflammatory markers, changes in lymphoid/myeloid cell ratios, and even signals of decreased biological age.

What is still unknown

This is not a full-text article, but a short abstract, so it does not contain all the methodological details: the exact IG mode, duration, design, sample size and statistics of the effect. We are waiting for a full-length publication to check the scale and reproducibility of the results.

Practical meaning (with reservations)

• IF is an “umbrella” over different protocols (time-restricted feeding, alternate-day fasting, etc.). In real life, it is better to start with soft regimes (e.g., a 12-14-hour “window” without food) and gradually adapt - especially for people 50+. Discuss dietary changes with your doctor if you have chronic diseases or take medications. Caution is required in case of diabetes (hypoglycemia), pregnancy, eating disorders.
• The point of IF is not “calorie punishment” but metabolic “switching” and recovery periods: reviews show that cycles of abstinence and refeeding affect immune cell signaling pathways and autophagy.

Conclusion

The new abstract adds another link to the evidence that intermittent fasting can “calm” inflammation and modulate innate immunity during aging, including by activating autophagy in macrophages. A full paper and independent replications are forthcoming to show how large and sustainable the effect is.

Source: Abstract Intermittent Fasting Improves Aging Immunity by Reprogramming Systemic Myeloid Lineage and Tissue Inflammation ( Current Developments in Nutrition, Suppl 2, May 2025), issue companion pages, and contextual reviews. DOI: 10.1016/j.cdnut.2025.106019