Study Spotlight Take-Away with Chef Dr. Mike: Aging, The Gut, and Diet

by Michael S. Fenster, MD

“I am perfect today but will improve tomorrow.”

― Shunryu Suzuki, Zen Mind, Beginner’s Mind

Immunosenescence refers to the gradual deterioration of the immune system associated with aging. This decline in immune function leads to a reduced ability to respond to infections, a higher incidence of diseases, and a decreased efficacy of vaccinations in older adults. Immunosenescence leads to various changes, such as a decrease in the production of new immune cells, a decline in the function of existing immune cells, and an increase in systemic inflammation.

But the rate at which this happens is not simply an inevitability of counting years. That is because physiologic age is more meaningful than chronological age. Physiologic aging, which refers to the biological changes that occur as we age, can be measured through various biomarkers and assessments. Biomarkers include things like telomere length, as the shortening of telomeres (the protective caps on the ends of chromosomes) is associated with cellular aging; DNA methylation patterns, often referred to as epigenetic clocks, reflect biological age, and increases in various inflammatory mediators like interleukin six (IL-6) and C-reactive protein (CRP) are associated with physiologic aging. Functional assessments such as gait speed, grip strength, and other measures of physical function and mobility in association with cognitive tests are valuable quantifiers of physiologic age. Measurements of things like bone density, brain MRI imaging, heart rate variability, and body composition can also add useful information regarding physiologic age. Previous columns have touched on other measures like intrinsic capacity and the frailty index.

The gut microbiome, a crucial factor in the status and functioning of the immune system, is intricately linked to many of the aforementioned biomarkers and assessments and no doubt plays a role in the aging process. It is also directly influenced by our dietary choices. While most discussions and almost all probiotic sales pitches focus on the bacterial components of the gut microbiota, the story is much larger. It extends beyond bacteria to a diverse range of viruses, which, as it turns out, may have a significant impact on healthy aging.

This week’s study examines the viral component of the gut microbiota, known as the gut virome, of centenarians, compared to cohorts of other ages.

The Study:

  • The study characterized the gut virome of 195 centenarians primarily from Japan (a group from Sardinia was also used for some analyses).
  • This was compared to the gut virome of a group of younger adults (those over 18 years of age) as well as a group of older adults (those over 60 years of age).

The Take-Away:

  • The gut virome of the centenarians was significantly more diverse than either group of adults and contained previously undescribed types of viruses.
  • The study focused on a type of virus known as a bacteriophage, which infects bacteria.
  • The changes to the gut microbiome of centenarians as a result of the types of viruses present resulted in alterations to sulfur metabolism with an “increased potential for converting methionine to homocysteine, sulfate to sulfide, and taurine to sulfide.”

The Caveat:

This study examined healthy aging in humans as reflected in their gut virome. Specifically, they examined the impact of a type of virus known as a bacteriophage, which specifically infects bacterial cells. Once the virus infects the bacterial cell, there are two different potential outcomes. One is known as the lytic cycle, and the other is referred to as the lysogenic cycle. These are how viruses replicate themselves within bacterial cells.

The lytic cycle consists of four phases. First, the virus attaches to the surface of the bacterium and injects its DNA into the bacterial cell. The viral, or phage DNA, then hijacks the bacterial cell’s machinery causing it to produce the necessary components – DNA, proteins, and enzymes – to make more viruses. These newly assembled viruses then cause cellular lysis. In this process, the bacterial cell ruptures so that the new viral phage particles are now free to infect other bacteria. The process of lysis causes the death of the bacterial cell

The other option, the lysogenic cycle, has some key differences. After entering the bacteria, the phage DNA integrates into the bacterial chromosome, and instead of hijacking the host DNA, it becomes part of it and what is known as a prophage. As the bacterium divides and makes more copies, the viral DNA, the prophage, is replicated along with the host bacterial DNA. During this period, the viral DNA remains dormant and causes no harm to its bacterial host. At some later time, in a process known as induction, under certain conditions, e.g., stress, the prophage can transform and enter into the lytic cycle lysing the host bacterium and releasing new viral bacteriophage particles as in the previous example.

During these quiescent periods, bacteriophage viruses may augment bacterial host metabolism by encoding auxiliary metabolic genes (AMGs). AMGs are genes involved in metabolic processes. Unlike typical viral genes that focus on the replication and assembly of new virions, AMGs modify the host cell’s metabolism to create a more favorable environment for viral replication. In other words, the AMGs act to boost the host’s survivability by altering the host’s metabolism, modifying nutrient pathways, or even modifying the host’s stress response.

A recent study utilizing a mouse model demonstrated that viral bacteriophages could influence the gut microbiota-brain axis affecting memory and cognition.[1] In the current study, there were alterations to the genes involved in sulfur metabolism. Such genes are critical for nucleic acid and protein synthesis. The centenarians exhibited a richer and more diverse viral population within their gut microbiome compared to younger cohorts. Their gut virome also contained 462 previously undescribed viruses. While this study does not demonstrate cause and effect, it does illustrate the complex interplay between all the diverse members of the gut microbiota, including viruses and their host organisms; both bacteria and us. Given that, at present, approximately 75% “of viral proteomes remain functionally unannotated,” it remains an undiscovered country and a reminder of how much we have yet to learn.

[1] (Mayneris-Perxachs, 2022)


Johansen, J., Atarashi, K., Arai, Y., Nobuyoshi, H., Soren, SJ., Vatanen, T., Knip, M., Honda, K., Xavier, RJ., Rasmussen, S., Plichta, DR. Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan. Nat Microbiol 8, 1064–1078 (2023).

Additional resources:

Howard-Varona, C., Lindback, M.M., Bastien, G.E., Solonenko, N., Zayed, AA., Jang, H., Andreopoulos, B., Brewer, HM., Glavina del Rio, T., Adkins, JN., Paul, S., Sullivan, MB., Duhaime, MB. Phage-specific metabolic reprogramming of virocells. ISME J 14, 881–895 (2020). Https://

Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, Garre-Olmo J, Puig J, Ramos R, Martínez-Hernández F, Burokas A, Coll C, Moreno-Navarrete JM, Zapata-Tona C, Pedraza S, Pérez-Brocal V, Ramió-Torrentà L, Ricart W, Moya A, Martínez-García M, Maldonado R, Fernández-Real JM. Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans. Cell Host Microbe. 2022 Mar 9;30(3):340-356.e8. doi: 10.1016/j.chom.2022.01.013.

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