Immune system modulation in aging: Molecular mechanisms and therapeutic targets

Cisneros, Bulmaro; García‐Aguirre, Ian; Unzueta, Juan; Arrieta‐Cruz, Isabel; González-Morales, Oscar; Domínguez-Larrieta, Juan M; Tamez-González, Aura; Leyva-Gómez, Gerardo; Magaña, Jonathan J

doi:10.3389/fimmu.2022.1059173

Cited by 27 publications

(28 citation statements)

References 88 publications

(116 reference statements)

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“…These findings are in line with previous reports highlighting the relevance of the endometrial-miometrial junctional zone in reproductive outcomes and changes in this region that take place with the aging process 27 . The immune system plays a crucial role in senescence and aging, leading to chronic inflammation (inflammaging) that disrupts cell/organ function 28 . Indeed, the process of myometrial senescence, carried by decreased proliferation and dysregulated gene expression in senescent cells 29 , 30 is patent in our results through an upregulation of genes such as JUN and FOS .…”

Section: Discussionmentioning

confidence: 99%

Effect of aging on the human myometrium at single-cell resolution

Punzon-Jimenez,

Machado-Lopez,

Perez-Moraga

et al. 2024

Nat Commun

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Age-associated myometrial dysfunction can prompt complications during pregnancy and labor, which is one of the factors contributing to the 7.8-fold increase in maternal mortality in women over 40. Using single-cell/single-nucleus RNA sequencing and spatial transcriptomics, we have constructed a cellular atlas of the aging myometrium from 186,120 cells across twenty perimenopausal and postmenopausal women. We identify 23 myometrial cell subpopulations, including contractile and venous capillary cells as well as immune-modulated fibroblasts. Myometrial aging leads to fewer contractile capillary cells, a reduced level of ion channel expression in smooth muscle cells, and impaired gene expression in endothelial, smooth muscle, fibroblast, perivascular, and immune cells. We observe altered myometrial cell-to-cell communication as an aging hallmark, which associated with the loss of 25 signaling pathways, including those related to angiogenesis, tissue repair, contractility, immunity, and nervous system regulation. These insights may contribute to a better understanding of the complications faced by older individuals during pregnancy and labor.

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Section: Discussionmentioning

confidence: 99%

Effect of aging on the human myometrium at single-cell resolution

Punzon-Jimenez,

Machado-Lopez,

Perez-Moraga

et al. 2024

Nat Commun

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“…WBS was grouped into two outcomes: ‘No clinical disease’ (WBS 0–0.5) and ‘Clinical disease’ (WBS 1–4) and included only those individuals identified to be shedding C. pecorum at the urogenital site at the time of sampling to ensure only infection-challenged individuals were included. As immune responses can vary across age groups, particularly in older individuals 10 , t -tests included age groups representing ‘adult’ (classes D–E) and ‘old’ koalas (classes F–I) with juvenile koalas (classes A–C) excluded due to inadequate sample size. PCs were first evaluated for normality and homogeneity of variance, and transformation performed if necessary.…”

Section: Methodsmentioning

confidence: 99%

A novel multi-variate immunological approach, reveals immune variation associated with environmental conditions, and co-infection in the koala (Phascolarctos cinereus)

Fernandez,

Krockenberger,

Valentina

et al. 2024

Sci Rep

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External signs of disease are frequently used as indicators of disease susceptibility. However, immune profiling can be a more effective indicator to understand how host responses to infection may be shaped by host, pathogen and environmental factors. To better inform wildlife health assessment and research directions, we investigated the utility of a novel multivariate immunophenotyping approach examining innate and adaptive immune responses in differing climatic, pathogen co-infection and demographic contexts across two koala (Phascolarctos cinereus) populations in New South Wales: the Liverpool Plains (LP), and Southern Highlands to South-west Sydney (SHSWS). Relative to the comparatively healthy SHSWS, the LP had greater and more variable innate immune gene expression (IL-1β, IL-6), and KoRV transcription. During extreme heat and drought, koalas from the LP displayed upregulation of a stress pathway gene and reduced adaptive immune genes expression, haematocrit and plasma protein, suggesting the possibility of environmental impacts through multiple pathways. In those koalas, KoRV transcription status, Chlamydia pecorum infection loads, and visible urogenital inflammation were not associated with immune variation, suggesting that immune markers were more sensitive indicators of real-time impacts than observed disease outcomes.

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“…There is some evidence for the involvement of these pathways in the regulation of lifespan across species, including human longevity. It is clear from the literature that manipulation of the DNA‐damage response and repair [100], the immune function [101] and telomere maintenance pathways [102] can result in changes in lifespan. Cholesterol metabolism, on the other hand, is strongly linked to human longevity via APOE .…”

Section: Current Approaches To Studying the Genetics Of Longevity In ...mentioning

confidence: 99%

Genetics of human longevity: From variants to genes to pathways

Smulders,

Deelen

2023

J Intern Med

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The current increase in lifespan without an equivalent increase in healthspan poses a grave challenge to the healthcare system and a severe burden on society. However, some individuals seem to be able to live a long and healthy life without the occurrence of major debilitating chronic diseases, and part of this trait seems to be hidden in their genome. In this review, we discuss the findings from studies on the genetic component of human longevity and the main challenges accompanying these studies. We subsequently focus on results from genetic studies in model organisms and comparative genomic approaches to highlight the most important conserved longevity‐associated pathways. By combining the results from studies using these different approaches, we conclude that only five main pathways have been consistently linked to longevity, namely (1) insulin/insulin‐like growth factor 1 signalling, (2) DNA‐damage response and repair, (3) immune function, (4) cholesterol metabolism and (5) telomere maintenance. As our current approaches to study the relevance of these pathways in humans are limited, we suggest that future studies on the genetics of human longevity should focus on the identification and functional characterization of rare genetic variants in genes involved in these pathways.

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Immune system modulation in aging: Molecular mechanisms and therapeutic targets

Cited by 27 publications

References 88 publications

Effect of aging on the human myometrium at single-cell resolution

Effect of aging on the human myometrium at single-cell resolution

A novel multi-variate immunological approach, reveals immune variation associated with environmental conditions, and co-infection in the koala (Phascolarctos cinereus)

Genetics of human longevity: From variants to genes to pathways

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