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Aging of the immune system

by luciano

Overview of the latest research on the aging immune system and its relationship with inflammation

Highlights
1 – Aging is a multifactorial process driven by various intrinsic and extrinsic factors, including genomic instability, telomere shortening (DNA sequence changes) [A], epigenetic alterations, loss of proteostasis, impaired macroautophagy, altered nutrient sensing [B], mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These factors are closely related to aging, and research has shown that inducing them can accelerate aging, while modifying them can slow, halt, or even reverse the aging process.
2 – Molecules secreted by senescent cells (senescence-associated secretory phenotype SASP [C]) promote chronic inflammation and can induce senescence in normal cells. At the same time, chronic inflammation accelerates the senescence of immune cells, resulting in weakened immune function and the inability to eliminate senescent cells and inflammatory factors, creating a vicious cycle of inflammation and senescence.

3 – Inflammaging [D] (chronic, low-grade, and persistent inflammation) is a recognized hallmark of aging, linked to morbidity and mortality. Inflammaging is so closely intertwined with the aging process that highly accurate aging clocks, predictive of morbidity and mortality, can be constructed using inflammatory markers.

4 – Although coniderable variability in aging exists among individuals, the aging process generally involves chronic inflammation, tissue homeostasis disorders, and dysfunction of the immune system and organ homeostasis disorders, and dysfunction of the immune system and organ functions, functions, readily causing cardiovascular, metabolic, autoimmune, and neurodegenerative diseases associated with aging.

5 – Gerotherapeutic interventions such as caloric restriction, ketogenic diet, or exercise may support healthspan in part by attenuating immune aging through unified immunometabolic mechanisms.

Researches

1 – The immune system offers a window into aging. 2025 Nature Aging.
The immune system permeates and regulates organs and tissues across the body, and has diverse roles beyond pathogen control, including in development, tissue homeostasis and repair. The reshaping of the immune system that occurs during aging is therefore highly consequential.
During aging, the ability of the immune system to efficiently and precisely respond to new antigenic, infectious or neoplastic challenges wanes, and the reactivation and refinement of memory responses falters. One of the earliest manifestations of aging is the involution of the thymus (the site of T cell development), which occurs during puberty. In later life, the immune system increasingly shifts from its homeostatic and protective roles towards a state that is char acterized by heightened proinflammatory activity, with a propensity for autoreactivity. Rather than safeguarding the host, the aged immune system may contribute to systemic dysfunction and pathology.

In this Focus, Nature Aging introduces a series of reviews and opinions that cover recent advances in immune aging. Building on their studies defining immune aging as a driver of organismal aging, Delgado-Pulido and colleagues explore how aging transforms the immune system ‘from healer to saboteur’, and describe the deterioration of protective functions and the acquisition of pathogenic features of the aged adaptive immune system.
Majewska and Krizhanovsky zoom in on one of these protective immune functions that declines with age: namely, the clearance of senescent cells. Through surveying the interactions between senescent and immune cells (which may deteriorate during aging), the authors highlight the role of the aged immune system in facilitating the accumulation and propagation of senescent cells across tissues with age, and thereby fueling tissue dysfunction and disease pathogenesis.
The effects of immune aging on age-related diseases are far-reaching. The fatal consequences of immune aging were demonstrated by impaired infection control during the COVID-19 pandemic. Immune aging has also been implicated in the pathogenesis of non-infectious age-related diseases, including cardiovascular, fibrotic and metabolic diseases, cancer and dementia. Indeed, both peripheral immunity and central neuroinflammation are recognized as contributors to, markers of and potential therapeutic targets in neurodegenerative conditions, and inflammaging is a recognized hallmark of aging linked to morbidity and mortalityrk. Pa and colleagues call attention to resident tissue macrophages as particular culprits of inflammaging and propose that restoring resident tissue macrophages by targeting the niche or myelopoiesis in the bone marrow could attenuate their contribution to tumori- genesis and promote healthy aging.
Inflammaging is so closely intertwined with organismal aging that highly accurate aging clocks, predictive of morbidity and mortality, can be built using markers of inflammation. Tracking individual immune aging trajectories could inform on disease risks as well as contribute to the suits of biological age-predictive biomarkers. However, both aging and the immune system hold considerable complexity and diversity. Franceschi and colleagues survey immune aging clocks through the lens of personalized inflammaging. They highlight that each individual’s unique combination of genetics, lifetime exposures and lifestyle factors results in heterogeneous manifestations of inflammaging, pose that precision measures and interventions should be prioritized, and spotlight a potential role for artificial intelligence in navigating this complexity.
Research on the biological processes of aging is often conducted using model organisms or in vitro models, yet thanks to the ease of access to human blood samples, the immune system offers a window into aging in humans. Immune aging can also be leveraged in clinical trials of aging, by testing the strength of vaccine responses or infection control. Trials that test emerging tech nologies or gerotherapeutic interventions could not only identify strategies to improve immune responses but also stand to inform our understanding of the plasticity of aging in humans and offer important milestones in refining the design of trials conducted with older adults. Discussing strategies to boost immune responses to vaccination in aging, Hofer and colleagues highlight the potential of enhancing vaccines by using gerotherapies to attenuate immune aging.
As well as providing an overview of the hallmarks of immune aging, Kim and Dixit further explore gerotherapeutic interventions, through an immunometabolic lens. They explore how gerotherapeutic interventions such as calorie restriction, ketogenic diet adoption or exercise may sustain healthspan in part through attenuation of immune aging via unified immunometabolic mechanisms. They also highlight adipose as an immunological organ with considerable physiological influence on aging.
Across these articles, the immune system stands out as an early target during aging: the loss of its protective capacities facilitates tissue degeneration and pathology. Weyand and Goronzy, however, highlight the acquisition of autoreactive functions during immune aging, and reflect on recent data that unexpectedly report an increase in autoimmune conditions with age. They propose that autoimmunity during aging constitutes inappropriate immune youthfulness and suggest that wan ing immune activity during aging could be beneficial in calibrating autoreactivity.
As a tractable and targetable window into aging in humans, the aged immune system holds opportunities for translationally valuable discoveries and constitutes a potential broad target to extend healthspan. We are very grateful to the authors and reviewers who have contributed to this issue. Our goal for this Focus has been to stimulate interest and promote cross-pollination of ideas across disciplines. We look forward to supporting immune aging research and sharing exciting findings from this field in the years to come.
References
1. Yousefzadeh, M. J. et al. Nature 594, 100–105 (2021).
2. Desdín-Micó, G. et al. Science 368, 1371–1376 (2020).
3. Bartleson, J. M. et al. Nat. Aging 1, 769–782 (2021).
4. Sarazin, M. et al. Nat. Aging 4, 761–770 (2024).
5. López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. Cell 186, 243–278 (2023).
6. Sayed N. et al. Nat. Aging 1, 598–615 (2021).
7. Conrad N. et al. Lancet 401, 1878–1890 (2023).
The immune system offers a window into aging. Volume 5; Agosto 2025 Nature Aging. https://doi.org/10.1038/s43587-025-00948-5

2 – Recent Advances in Aging and Immunosenescence: Mechanisms and Therapeutic Strategies. Shuaiqi Wang1 . Cell. 2025

Introduction
Population aging is currently one of the major global challenges [1]. With the intensification of population aging, delaying aging and improving the quality of life for elderly people have become important tasks. Aging is a multifactorial process driven by various intrinsic and extrinsic factors, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis [2]. These factors are closely related to organismal aging, and research has shown that inducing them can accelerate aging, while intervening in them can slow down, halt, or even reverse the aging process [2]. Thoroughly studying these aging factors to elucidate the mechanisms of aging can help identify interventions to delay aging, such as caloric restriction, nutritional interventions, and gut microbiota transplantation, as well as clinical treatments for aging-related diseases, eases, including senolytics, stem cell therapy, and antioxidant and anti-inflammatory including senolytics, stem cell therapy, and antioxidant and anti-inflammatory treatments.
These approaches can mitigate aging and aging-related diseases, thereby achieving healthy achieving healthy aging and longevity [3–5].
Among these factors, cellular senescence is a key contributor to organismal aging. Targeting senescent cells (SCs) holds promise for developing novel and practical antiaging therapies [6]. Cellular senescence is an irreversible state of cell cycle arrest caused by varivarious factors, such as DNA damage and telomere shortening [7,8]. Additionally, the process whereby immune system function gradually declines or becomes dysregulated whereby immune system function gradually declines or becomes dysregulated with human aging is known as immunosenescence [E] [9]. Although coniderable variability in aging exists among individuals, the aging process generally involves chronic inflammation, tissue homeostasis disorders, and dysfunction of the immune system and organ homeostasis disorders, and dysfunction of the immune system and organ functions, [2] functions, [2] readily causing cardiovascular, metabolic, autoimmune, and neurodegenerative diseases associated with aging [5,10–13]. Existing research indicates that transplanting SCs into young mice induces bodily dysfunction, while transplanting them into aged mice exacerbates aging and increases the risk of death [6].
This suggests that SCs accelerate organismal aging. The specific reason is that SCs release the senescence-associated secretory phenotype (SASP) into the tissue, promoting chronic inflammation and inducing senescence in surrounding tissue cells and immune cells [14]. SCs and chronic inflammation interact and crosstalk, forming a vicious cycle of inflammation and aging.
Therefore, in-depth research into the key characteristics and underlying mechanisms of cellular senescence, immunosenescence, and inflammation, identifying drug intervention targets, and developing targeted interventions can help mitigate aging and aging-related diseases, thereby promoting healthy aging in the elderly. In recent years, based on the establishment of a series of aging-related cellular and animal models (Table 1), the latest research has revealed the molecular mechanisms of cellular senescence and immunosenescence and the body’s regulation of aging from an immune response perspective.
Moreover, based on new mechanisms, strategies targeting the elimination of SCs have become a promising treatment method for alleviating aging and age-related diseases.
Later, it was discovered that some that small-molecule senolytic senolytic drugs target proteins in cell senescent antiapoptotic pathways (SCAPs) can selectively kill SCs (Figure 1).
Currently, effective, safe, and selective immunotherapy selective approaches targeting SCs are becoming promising a treatment method. Some teams research have teams have already already developed senolytic CAR T cells [19], senolytic vaccines [20], and immune checkpoint blockade (ICB) therapies to achieve the clearance of SCs [21].

Figure 1. 1. Cellular Cellular senescence and senolytics. SCs continuously produce numerous pro-inflammatory senescence and senolytics. SCs continuously produce numerous pro-inflammamolecules and tissue-remodeling molecules, known as the SASP, which further accelerates the aging tory molecules and tissue-remodeling molecules, known as the SASP, which further accelerates the process. Senolytics promote the regeneration of new healthy cells by identifying and clearing SCs. Created with BioRender.com (accessed on 10 May 2024).

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Summary and Prospects
The global issue of population aging is becoming increasingly severe, with elderly individuals being more susceptible to infections and age-related diseases, leading to higher morbidity and mortality rates [5]. Cellular senescence and immunosenescence are closely linked to aging; therefore, this review focuses on immunotherapies targeting aging. It revisits significant recent discoveries in the mechanisms of cellular senescence and immunosenescence that have propelled the development of new treatment paradigms for aging and age-related diseases.
Recent Advances in Aging and Immunosenescence: Mechanisms and Therapeutic Strategies. Shuaiqi Wang1 . Cell. 2025
Department of Immunology, CAMS Key Laboratory T-Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Common Mechanism Research for Major Diseases, Beijing 100005, China; b2023005058@pumc.edu.cn (S.W.); huotong1998@pumc.edu.cn (T.H.); b2022005055@student.pumc.edu.cn (M.L.); s2022005053@student.pumc.edu.cn (Y.Z.); zhangjianmin@ibms.pumc.edu.cn (J.Z.). https://doi.org/10.3390/cells14070499

3 – Chronic Low-Grade Inflammation and Brain Structure in the Middle-Aged and Elderly Adults. 2024
Abstract: Low-grade inflammation (LGI) mainly acted as the mediator of the association of obesity and inflammatory diet with numerous chronic diseases, including neuropsychiatric diseases. However, the evidence about the effect of LGI on brain structure is limited but important, especially in the context of accelerating aging. This study was then designed to close the gap, and we leveraged a total of 37,699 participants from the UK Biobank and utilized inflammation score (INFLA-score) to measure LGI. We built the longitudinal relationships of INFLA-score with brain imaging phenotypes using multiple linear regression models. We further analyzed the interactive effects of specific covariates. The results showed high level inflammation reduced the volumes of the subcortex and cortex, especially the globus pallidus ( β [95% confidence interval] = −0.062 [−0.083, −0.041]), thalamus (−0.053 [−0.073, −0.033]), insula (−0.052 [−0.072, −0.032]), superior temporal gyrus (−0.049 [−0.069, −0.028]), lateral orbitofrontal cortex (−0.047 [−0.068, −0.027]), and others. Most significant effects were observed among urban residents. Furthermore, males and individuals with physical frailty were susceptive to the associations. The study provided potential insights into pathological changes during disease progression and might aid in the development of preventive and control targets in an age-friendly city to promote great health and well-being for sustainable development goals.

Figure 1. Study workflow.Figure 1. Study workflow. We screened 37,699 UK Biobank participants to explore the effects of
We screened 37,699 UK Biobank participants to explore the effects of low-
grade inflammationlow-grade(LGI) oninflammation (LGI) on thd brain system, and the exclusion criteria of our study population
thd brain system, and the exclusion criteria of our study population is
shown in pane (A).is shownAdditionally,in pane we(A).usedAdditionally,the weINFLA-score,used thecharacterizedINFLA-score, bycharacterizedC-reactivebyprotein,C-reactive protein, white blood cell, plateletwhite bloodcounts,cell,andplateletneutrophil-to-lymphocytecounts, and neutrophil-to-lymphocyteratio, to measureratio,andto measurequantifyandthequantify the levels of LGI, and relevantlevels of LGI,informationand relevantas showninformationin paneas shown(B). Asinshownpane (B).inAspaneshown(C),intakingpane (C),influen-taking influential tial factors of LGI intofactorsaccount,of LGIweintofit theaccount,multiplewe fitlinearthe multipleregressionlinearmodelregressioncontrollingmodel forcontrollingcovariatesfor covariates (age, sex, IMD, WHR,(age,healthysex, IMD,lifestyle,WHR, healthyprevalencelifestyle,of hypertension,prevalence of hypertension, diabetes mellitus and stroke)
diabetes mellitus and stroke)
and conducted subgroupand conductedanalysis bysubgroupage, sex,analysisWHR,bymetabolicage, sex,syndrome,WHR, metabolicphysicalsyndrome,frailty. Thephysicalmainfrailty. The results demonstratedmaina significantresults demonstratedassociationa ofsignificantLGI withassociationatrophyofofLGIbrainwithregions,atrophy ofincludingbrain regions,sub- including cortex, frontal lobe,subcortex,temporalfrontallobe, parietallobe, temporallobe andlobe,insulaparietallobe.lobe and insula lobe.

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Conclusions
To sum up, the conceptual and design framework of our investigation is to characterize the associations between LGI and brain imaging phenotypes, thus showing that LGI may lead to subclinical cognitive decline or neuropsychic diseases partly via structural neural pathways. Moreover, our analyses revealed that more significant associations of LGI with the atrophy of brain structure among male or individuals with physical frailty. These findings not only contribute to the evolvement of clinical diagnosis and therapy, but also provide a novel perspective for the development of new preventive strategies, namely, when brain lesions are subclinical and without any apparent clinical sign, inflammatory intervention, such as diet therapy, is an early preventive strategy.
Chronic Low-Grade Inflammation and Brain Structure in the Middle-Aged and Elderly Adults. Yujia Bao et al. School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; bubble-y@sjtu.edu.cn (Y.B.); c.cctx@sjtu.edu.cn (X.C.); melody321@sjtu.edu.cn (Y.L.); scp-173@sjtu.edu.cn (S.Y.). Nutrients 2024, 16, 2313. https:// doi.org/10.3390/nu16142313

Vitamin D eand vitamin C promoting healthy ageing

by luciano

Overview. Both Vitamin D and Vitamin C contribute to intestinal barrier health by supporting the function of tight junctions and promoting repair. Vitamin D, through its receptor (VDR), regulates proteins that form tight junctions, which maintain barrier integrity and modulate the immune system. Vitamin C can also promote barrier repair, potentially through regulating Notch signaling pathways and by influencing the gut microbiome composition, which can further support the barrier.
Vitamin D’s Role
Tight Junctions:
The active form of Vitamin D, 1,25(OH)2D3, regulates the expression of proteins like claudins and ZO within the tight junction complex, which are crucial for maintaining and repairing the intestinal barrier.
Immune Modulation:
Vitamin D binds to VDR in immune cells and modulates immune responses, helping to protect against conditions that can compromise the barrier, like inflammatory bowel disease.
Barrier Integrity:
By binding to VDRs and affecting immune cells and epithelial cells, Vitamin D signaling helps maintain a healthy, stable intestinal barrier.
Vitamin C’s Role
Barrier Repair:
Vitamin C supplementation has demonstrated beneficial effects on the intestinal barrier, helping to repair damage.
Notch Signaling:
Combined with Vitamin D, Vitamin C may regulate the Notch signaling pathway to protect the intestinal mucosal barrier, including the expression of claudin-2.
Gut Microbiome:
Vitamin C supplementation can help balance the gut microbiota in healthy individuals with suboptimal Vitamin C levels, which may indirectly benefit the barrier by reducing the presence of potentially harmful LPS-producing bacteria.
Combined Effects
Synergistic Protection:
Research indicates that combining Vitamin C and Vitamin D may offer greater protective effects on the intestinal barrier compared to either vitamin alone, possibly through their combined influence on the Notch signaling pathway.
Therapeutic Potential:
Both vitamins are being investigated for their potential in managing intestinal diseases by enhancing barrier integrity and modulating the immune response within the gut.

Researches
1 – Gut-interplay: key to mitigating immunosenescence and promoting healthy ageing. 2025
Abstract
Background Immunosenescence is the loss and change of immunological organs, as well as innate and adaptive immune dysfunction with ageing, which can lead to increased sensitivity to infections, age-related diseases, and cancer. Emerging evidence highlights the role of gut-vitamin D axis in the regulation of immune ageing, influencing chronic inflammation and systemic health. This review aims to explore the interplay between the gut microbiota and vitamin D in mitigating immunosenescence and preventing against chronic inflammation and age-related diseases.
Main text
Gut microbiota dysbiosis and vitamin D insufficiency accelerate immunosenescence and risk of chronic diseases. Literature data reveal that vitamin D modulates gut microbiota diversity and composition, enhances immune resilience, and reduce systemic inflammation. Conversely, gut microbiota influences vitamin D metabolism to promote the synthesis of active vitamin D metabolites with implications for immune health.
Conclusions
These findings underscore the potential of targeting gut-vitamin D axis to modulate immune responses, delay the immune ageing, and mitigate age-related diseases. Further research is needed to integrate vitamin D supplementation and microbiome modulation into strategies aimed at promoting healthy ageing.
Keywords Gut microbiota, Vitamin D, Immune ageing, Immunosenescence, Healthy ageing
Gut-vitamin D interplay: key to mitigating immunosenescence and promoting healthy ageing. 2025. Hammad Ullah. https://doi.org/10.1186/s12979-025-00514-y
Hammad Ullah hammadrph@gmail.com 1 School of Pharmacy, University of Management and Technology, Lahore 54000, Pakistan

2 – Perspectives About Ascorbic Acid to Treat Inflammatory Bowel Diseases. Ian Richard Lucena Andriolo et al. 2024.

It is known that reactive oxygen species cause abnormal im- mune responses in the gut during inflammatory bowel dis- eases (IBD). Therefore, oxidative stress has been theorized as an agent of IBD development and antioxidant compounds such as vitamin C (L-ascorbic acid) have been studied as a new tool to treat IBD. Therefore, the potential of vitamin C to treat IBD was reviewed here as a critical discussion about this field and guide future research. Indeed, some preclinical studies have shown the beneficial effects of vitamin C in models of ulcerative colitis in mice and clinical and experimental findings have shown that deficiency in this vitamin is associated with the de- velopment of IBD and its worsening. The main mechanisms that may be involved in the activity of ascorbic acid in IBD in- clude its well-established role as an antioxidant, but also others diversified actions. However, some experimental studies em- ployed high doses of vitamin C and most of them did not per- form dose-response curves and neither determined the mini- mum effective dose nor the ED50. Allometric extrapolations were also not made. Also, clinical studies on the subject are still in their infancy. Therefore, it is suggested that the research agenda in this matter covers experimental studies that assess the effective, safe, and translational doses, as well as the ap- propriate administration route and its action mechanism. After that, robust clinical trials to increase knowledge about the role of ascorbic acid deficiency in IBD patients and the effects of their supplementation in these patients can be encouraged.
Perspectives and conclusion
The pathogenesis of IBD is closely related to oxidative stress due to an intense inflammatory insult and the use of vitamin C in IBD, as well as the role of its deficiency, is currently being investigated. Therefore, this perspective reviewed the pharmacological poten- tial of this vitamin to treat and prevent these diseases. In this ap- proach, Vitamin C may help the integrity of the intestinal barrier under the inflammatory stimulus, and enhance intestinal mucosal barrier function, while reducing oxidative stress.
However, a point that is worthy of attention in non-clinical stud- ies presented here is the dose used, which must be adequate for extrapolation in humans. Studies suggest that a daily intake of vi- tamin C from 100 to 400 mg promotes 100 % of the bioavailability and reaches a maximum serum content of 70–80 µmol/L [33, 34]. In addition, when the intake of vitamin C exceeds 500 mg/day, a further increase in plasma concentration is inhibited and when doses greater than 1,000 mg of ascorbic acid are administered in a single dose the bioavailability can decrease by 30 % [34]. This oc- curs because when 500–1,000 mg of vitamin C are administered orally, the intestinal transporter quickly achieves its maximal satu- ration, while the vitamin is progressively excreted by urine [34, 35].
Another important point, which has not yet been studied, is the impact of the pH of the ascorbic acid solution used in the experi- mental studies. Since the pH of an ascorbic acid solution is very low it is expected that its administration can reduce the pH at the in- jection site, intestine, and colon if an enema was used. So, further studies need to address this bias and evaluate the use of buffered ascorbic acid solutions. Perspectives About Ascorbic Acid to Treat Inflammatory Bowel Diseases. Ian Richard Lucena Andriolo et al. 2024. DOI 10.1055/a-2263-1388. ISSN 2194-9379

3 – Vitamin D Receptor Influences Intestinal Barriers in Health and Disease. Jun Sun and Yong-Guo Zhang. 2022.
Abstract:
Vitamin D receptor (VDR) executes most of the biological functions of vitamin D. Beyond this, VDR is a transcriptional factor regulating the expression levels of many target genes, such as genes for tight junction proteins claudin-2, -5, -12, and -15. In this review, we discuss the progress of research on VDR that influences intestinal barriers in health and disease. We searched PubMed and Google Scholar using key words vitamin D, VDR, tight junctions, cancer, inflammation, and infection. We summarize the literature and progress reports on VDR regulation of tight junction distribution, cellular functions, and mechanisms (directly or indirectly). We review the impacts of VDR on barriers in various diseases, e.g., colon cancer, infection, inflammatory bowel disease, and chronic inflammatory lung diseases. We also discuss the limits of current studies and future directions. Deeper understanding of the mechanisms by which the VDR signaling regulates intestinal barrier functions allow us to develop efficient and effective therapeutic strategies based on levels of tight junction proteins and vitamin D/VDR statuses for human diseases.
Conclusions
The recent progress reveals a novel activity of VDR in regulation of many tight junction proteins in primate cell structure and intestinal homeostasis and diseases (as shown in the Graphic Abstract). We aim to show the current state of knowledge on this topic and its potential therapeutic applications. This knowledge can be used to develop intestinal VDR-associated TJ proteins, e.g., claudin-5 and -15, as clinical biomarkers for identifying patients who may benefit from currently available interventions and could be used for the eventual development of novel strategies for the prevention and treatment of diseases. VDR signaling is also highly significant in regulating other proliferation and anti-inflammatory pathways [74 ,157 , 162 ,174 ]. We hope to integrate our findings with other studies and, more importantly, understand how the microbiome, probiotics, and metabolites coordinate the effects of vitamin D/VDR [ 146 ]. Our long-term goal is to develop individualized therapeutic strategies based on tight junction proteins [ 175 ] and vitamin D/VDR statuses for efficient and effective prevention and treatment of chronic diseases.
Vitamin D Receptor Influences Intestinal Barriers in Health and Disease
Jun Sun 1,2,3,* and Yong-Guo Zhang 1.
1 Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; yongguo@uic.edu; 2 Department of Microbiology/Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA; 3 Jesse Brown VA Medical Center Chicago (537), 820 S Damen Ave, Chicago, IL 60612, USA. Cells 2022, 11, 1129. https://doi.org/10.3390/cells11071129.

Immunology of chronic low-grade inflammation: relationship with metabolic function

by luciano

Inflammation is part of the body’s innate immune response and is an essential process that not only defends against harmful bacteria and pathogens but also plays a key role in the maintenance and repair of tissues. Under pathological conditions, there is bilateral crosstalk between immune regulation and aberrant metabolism resulting in persistent inflammation in the absence of infection. This phenomenon is referred to as sterile metabolic inflammation (metainflammation) and occurs if the initiating stimulus is not removed or if the resolution process is disrupted.
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This low-grade chronic metabolic inflammation should not be neglected as it is significantly associated with all-cause mortality in the general population (Fest et al. 2019), negatively impacts insulin sensitivity (Blaszczak et al. 2020), and increases the risk for cancer development (Li et al. 2023).
Immunology of chronic low-grade inflammation: relationship with metabolic function. Mari van de Vyver. Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Journal of Endocrinology (2023) 257, e220271

Note:
1 – Metabolic function refers to the continuous chemical processes within cells and organisms that convert food into usable energy, build and repair tissues, and sustain life. This includes vital processes like breathing, blood circulation, and cell maintenance, even during rest. The two main categories of metabolic reactions are anabolism, which builds larger molecules and uses energy, and catabolism, which breaks down larger molecules to release energy, such as the digestion of food

2 – Inflammation immunology describes the immune system’s response to tissue damage or infection, an innate, nonspecific defense mechanism that serves to eliminate harmful agents and promote repair. Inflammation, or inflammation, involves immune cells and molecules drawing more blood to the damaged site, causing redness, heat, swelling, and pain. While a protective process, excessive or chronic inflammation can become harmful and contribute to autoimmune diseases or other conditions.

Hydrocolloids and Food Emulsifiers II part

by luciano

C – Hydrocolloids also modulate gut microbiota, offering various health benefits. Certain hydrocolloids, such as inulin and pectin, act as prebiotics, promoting beneficial gut bacteria growth and influencing microbiota composition and diversity (Bouillon et al., 2022; Gularte & Rosell, 2011).

D – Hydrocolloids are long-chain hydrophilic polymers used in food systems for thickening, gelling, and stabilization. They significantly influence starch retrogradation, hydrolysis, and modulation of the gut microbiota, with both positive and negative effects. These effects depend on factors such as the type of hydrocolloid, its concentration, interactions with starch, and environmental conditions such as temperature and processing methods. Some hydrocolloids inhibit starch retrogradation by interrupting amylose recrystallization, while others promote it under certain conditions. They can also alter starch hydrolysis by modifying the accessibility of enzymes to starch granules, slowing or accelerating digestion. Furthermore, hydrocolloids act as fermentable fibers, promoting the growth of beneficial gut bacteria, which can influence metabolic processes. Despite significant advances, the complexity of these interactions remains incomplete, as the effects vary depending on the composition of the individual microbiota. This review explores the mechanisms by which hydrocolloids modulate starch behaviors and the gut microbiota, synthesizing the current literature and identifying future research directions to address existing knowledge gaps.
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In food systems, hydrocolloids influence starch retrogradation, starch hydrolysis, and gut microbiota modulation, essential factors for both food quality and human health.
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Several hydrocolloids, including xanthan gum, pectin, β-glucan, and konjac glucomannan, influence starch hydrolysis and reduce its digestibility. Their effects depend on their molecular structure, source, concentration, interactions with starch, and processing conditions (Ma et al., 2024). By increasing the viscosity of starch-based matrices, hydrocolloids create a resistant gel network, slowing the enzymatic degradation of starch in the gastrointestinal tract. This delayed hydrolysis results in a controlled glucose release and a lower postprandial glycemic response (Bae & Lee, 2018; Bellanco et al., 2024). Consequently, hydrocolloids have the potential to improve glycemic control and reduce the risk of metabolic disorders such as type 2 diabetes. Yassin et al. (2022) reported that incorporating xanthan gum, lambda-carrageenan, or psyllium husk (1–5% w/w of flour weight) into white bread significantly reduced glycemic potency, with psyllium husk at 5% w/w exerting the strongest effect. Similarly, Mæhre et al. (2021) found that white bread fortified with guar gum reduced postprandial glycemic responses.
Hydrocolloids also modulate the gut microbiota, offering several health benefits. Some hydrocolloids, such as inulin and pectin, act as prebiotics, promoting the growth of beneficial gut bacteria and influencing the composition and diversity of the microbiota (Bouillon et al., 2022; Gularte & Rosell, 2011). Their prebiotic effects depend on their physicochemical properties, with variations in polymeric structure and source influencing gut health outcomes (Ağagündüz et al., 2023). Reported benefits include improved digestion, enhanced immune function, and reduced inflammation, although the extent and mechanisms of these effects remain inconsistent in the literature (Zhang et al., 2023). Further research is needed to fully understand both the benefits and potential limitations of hydrocolloid applications for gut health. This review provides an in-depth analysis of the effects of hydrocolloids on starch retrogradation, digestibility, and the gut microbiota, addressing both positive and negative findings, and aims to inform the development of functional foods with improved health benefits. The multifunctional role of hydrocolloids in modulating retrogradation, starch hydrolysis, and the gut microbiota. Xikun Lu et al. Food Chemistry
Volume 489, 15 October 2025, 144974.

Hydrocolloids and Food Emulsifiers I part

by luciano

Introduction
Hydrocolloids and emulsifiers are both food additives, but they have different functions. Hydrocolloids are substances that thicken, gel, or stabilize foods, while emulsifiers help mix immiscible substances like oil and water.

Hydrocolloids
Are substances that, in aqueous solution, form a colloidal system, increasing viscosity or forming gels.Their main function is to modify the consistency of foods, making them thicker, creamier, or gelatinous. They can also stabilize emulsions or suspensions, preventing phase separation.
Some examples of hydrocolloids: agar-agar, modified starches, beta-glucans, carrageenans, pectin, carob seeds, bamboo fibers, potato fibers, pea fibers, gelatins, gum arabic, xanthan gum, guar gum, and inulin. In which products are they most likely to be found: baked goods and pastries, biscuits, ice cream, yogurt, sports drinks (especially maltodextrin

Emulsifiers:
They are molecules that have a hydrophobic (fat-loving) portion and a hydrophilic (water-loving) portion. This structure allows them to stabilize emulsions, which are mixtures of immiscible liquids such as oil and water. Emulsifiers sit between the two phases, reducing surface tension and preventing separation. Common examples include lecithin, mono- and diglycerides of fatty acids, and polysorbates.
In short, while hydrocolloids modify the overall texture of a food, emulsifiers work specifically to keep emulsions stable, preventing the separation of oil and water. Some hydrocolloids, such as lecithin, can also have emulsifying properties.

Hydrocolloids

A -Hydrocolloids enable products with long shelf lives, the inclusion of whole grain flours and fiber, the absence of trans fats, and, last but not least, the absence of gluten. Hydrocolloids are molecules capable of binding water in large quantities; among the most commonly used in baked goods are xanthan gum, pectin, modified cellulose, and fructo- and galacto-oligosaccharides. Some of these substances are considered dietary fibers, capable of stimulating a feeling of satiety and having positive effects on intestinal function. Hydrocolloids often achieve their technological-functional effect in the product even when added to dough in small quantities, for example, less than 1% of the total powdered ingredients. In bread dough and other baked goods, hydrocolloids help improve dough workability during production thanks to their rapid and uniform hydration. The volume, structure, and softness of the finished products are improved.
Fragility is reduced, for example, in the case of “foamy” baked goods with a high presence of air bubbles or suspended particles (chocolate, fruit, or nuts): these bubbles or particles are stabilized within the system thanks to hydrocolloids. During storage, the shelf life of the products is also increased by maintaining their softness for longer periods: the difference compared to products without hydrocolloids becomes more evident as time passes. Finally, it appears that the presence of hydrocolloids is also able to influence the size of ice crystals within bread dough or other semi-cooked products during freezing, resulting in a higher-quality thawed product (Reference H1).
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There are unit operations that are difficult to implement for foods that do not involve the use of gluten, such as the extrusion, drawing, or lamination phases that occur in pasta or some baked goods. The stresses that occur in these phases require elasticity in the dough, therefore, formulations capable of withstanding the continuous processing of a perhaps pre-existing plant are essential (Reference H2).
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Comparing gluten-free crackers, we find extremely simple formulations, with corn and rice flours, and more complex ones, with the addition of potato starch, dextrose, emulsifiers, and thickeners. From a nutritional standpoint, it’s clear that the food may be richer in sugars and some fats than the same conventional product. Sandwich bread, more difficult to make because it’s leavened, features rather complex formulations based on corn, rice, or buckwheat, starches, vegetable fibers, proteins, sugars, thickeners (including hydrocolloids), emulsifiers, and acidifiers. This recipe implies, nutritionally, either an increase in carbohydrates of approximately 10-15% compared to the conventional product in the same category, or an increase in fats, especially saturated fats, of approximately 30-50% (Reference H3).
In the confectionery sector, the considerations are more or less the same, since from a nutritional point of view, compared to conventional products, they remain higher values of carbohydrates, especially sugars, and fats, mainly saturated, to compensate for the lack of viscoelasticity of the protein part. Prodotti e tecnologie per alimenti senza glutine. Macchine alimentari – Anno XVII -1 – Genn. Feb 2015

B – The food industry has been committed to providing consumers with high-quality rheological properties along with healthy and nutritious food products (Goff & Guo, 2019; Manzoor, Singh, Bandral, Gani, & Shams, 2020). Consequently, recent years have seen the widespread use of food hydrocolloids in the formulation/reformulation of various food categories, the production of functional foods, and innovation initiatives (Manzoor et al., 2020). Food hydrocolloids are considered crucial food components due to their improvements in viscosity, gelation, and thickening, enhancing the rheology and sensory properties of foods (Saha & Bhattacharya, 2010; Goff & Guo, 2019). The terms gum and mucilage may also be used interchangeably with hydrocolloids. Regardless of what they are called, these ingredients are generally found in industrial applications as viscosity improvers, emulsifiers, coating agents, gelling agents, stabilizing agents, and thermodynamic stability providers (Goff & Guo, 2019; Maity, Saxena e Raju, 2018; Manzoor et al., 2020) (Fig. 1).
They find functional applications mainly in food products, including confectionery (glazing agents, texturizers), specific beverages (emulsifiers), dairy products (thickeners and stabilizers), pastries (bulking agents, sensory quality and shelf-life improvers), and frozen fruits and vegetables (cryoprotectant) (Maity et al., 2018; Salehi, 2020; Viebke, Al-Assaf, and Phillips, 2014). Recently, food-grade hydrocolloids have reached the forefront due to their health benefits and significant pharmaceutical, as well as food, applications. Furthermore, their potential health effects and the mechanisms of their dietary intake have been studied.
Recent literature has indicated that dietary hydrocolloids play crucial roles on the gut microbiota due to their diverse physicochemical or structural properties (Tan & Nie, 2021). Some of these important roles are their prebiotic impacts, stimulating the production of short-chain fatty acids (SCFA), reducing gastrointestinal discomfort as well as preserving normal intestinal function (Marciani et al., 2019; Viebke et al., 2014; Williams & Phillips, 2021, pp. 3–26), an increase in viscosity within the intestinal lumen, a reduction or increase in the absorption of some nutrients (Nybroe et al., 2016), lower cholesterol (Manzoor et al., 2020; McClements, 2021), a decrease in hyperglycemia (Lu, Li, & Fang, 2021) as well as normal body weight regulation (Johansson, Andersson, Alminger, Landberg, & Langton, 2018; Viebke et al., 2014). Furthermore, research on hydrocolloids and intestinal modulation appears to be expanding day by day thanks to cutting-edge multi-omics technologies and detailed analysis of the human microbiome. This article provides a comprehensive overview of specific dietary hydrocolloids, particularly those with a polysaccharide structure in intestinal modulation, and their potential interactions with nutrition and health.
A comprehensive review on food hydrocolloids as gut modulators in the food matrix and nutrition: The hydrocolloid-gut-health axis. al. 2023. https://doi.org/10.1016/j.foodhyd.2023.10906