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Review
. 2022 Sep;21(9):e13700.
doi: 10.1111/acel.13700. Epub 2022 Aug 24.

A gut-centric view of aging: Do intestinal epithelial cells contribute to age-associated microbiota changes, inflammaging, and immunosenescence?

Leah S Hohman  1 , Lisa C Osborne  1
Affiliations
Review

A gut-centric view of aging: Do intestinal epithelial cells contribute to age-associated microbiota changes, inflammaging, and immunosenescence?

Leah S Hohman et al. Aging Cell. 2022 Sep.

Abstract

Intestinal epithelial cells (IECs) serve as both a physical and an antimicrobial barrier against the microbiota, as well as a conduit for signaling between the microbiota and systemic host immunity. As individuals age, the balance between these systems undergoes a myriad of changes due to age-associated changes to the microbiota, IECs themselves, immunosenescence, and inflammaging. In this review, we discuss emerging data related to age-associated loss of intestinal barrier integrity and posit that IEC dysfunction may play a central role in propagating age-associated alterations in microbiota composition and immune homeostasis.

Keywords: aging; immunosenescence; inflammaging; intestinal epithelial cells; microbiome.

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Conflict of interest statement

The authors have no conflicts to declare.

Figures

FIGURE 1
FIGURE 1
Hallmarks of inflammaging and immunosenescense in both humans and mice
FIGURE 2
FIGURE 2
Impact of the age of the microbiota on inflammaging outcomes. Transfer of an aged microbiota is sufficient to elicit aspects of an inflammaging phenotype in young mice, including increases in circulating inflammatory cytokines and impaired phagocytosis. Conversely, aged germ‐free (GF) mice are resistant to inflammaging, and transfer of young microbiomes can reverse some aspects of immune homeostasis in conventionally raised aged mice
FIGURE 3
FIGURE 3
Intestinal epithelial cells at the intersection of environmental factors, the microbiota, and immunity. During the aging process, immune cells, gut microbial composition, and intestinal epithelial cells are each impacted by a multitude of factors including environmental factors (geography, immunological exposure, infection history, medical history (type of birth, antibiotic use, etc)), age, sex, and genetics. The tripartite communication between these systems could be manipulated to promote healthy aging outcomes
FIGURE 4
FIGURE 4
Changes in IEC differentiation during the aging process. Aging results in silencing of the stem cell marker Lgr5, resulting in a reduction in Wnt signaling and iESC regenerative capacity. Notch1‐mediated inhibition of Atoh1 regulates the differentiation of secretory IECs and maintains balanced differentiation of IEC subtypes in healthy human adults. Decreased expression of Notch1 with age results in a corresponding increase of Atoh1 and preferential skewing toward secretory IEC fate
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