Cellular senescence and the host immune system in aging and age-related disorders

Giannoula, Yvonne; Kroemer, Guido; Pietrocola, Federico

doi:10.1016/j.bj.2023.02.001

Cited by 28 publications

(18 citation statements)

References 100 publications

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Section: Discussionmentioning

confidence: 99%

“…Evidence increasingly links cellular senescence with the individual aging trajectory and age-related diseases 42,43 . Whereas the immune system is central to clearing SCs and maintaining tissue homeostasis 5,44 , the mechanisms through which the immune system modulates SCs remain elusive. Here, we found that a specific subset of CD4 T cells, known as CD4 CTLs, that accumulate with aging played a significant role in restricting cellular senescence and frailty.…”

Section: Discussionmentioning

confidence: 99%

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CD4 T Cells Acquire Cytotoxic Properties to Modulate Cellular Senescence and Aging

Elyahu,

Feygin,

Pinkas

et al. 2024

Preprint

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Aging is characterized by the progressive deterioration of tissue structure and function, leading to increased vulnerability to diseases and, eventually, death. One prominent process in aging is the accumulation of senescent cells. Although the immune system has been recognized as crucial for the elimination of senescent cells, the associated mechanisms remain incompletely understood. Here we show that CD4 T cells differentiate into cytotoxic T lymphocytes (CTLs) in a senescent cell-rich environment and that a reduction in the senescent cell load, achieved using chemical senolytic drugs, was sufficient to halt this differentiation. We further demonstrate that eliminating CD4 CTLs in the context of late aging by selectively deleting the Eomes transcription factor in CD4 T cells resulted in the increased accumulation of senescent cells, profound physical deterioration, and a decreased life span. In liver cirrhosis, a model of localized chronic inflammation, CD4 CTL elimination increased the senescent load and worsened the disease. Collectively, our findings demonstrate the fundamental role of CD4 CTLs in modulating tissue senescence and unveil a new aspect of age-related T-cell biology implicated in disease susceptibility and longevity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CD4 T Cells Acquire Cytotoxic Properties to Modulate Cellular Senescence and Aging

Elyahu,

Feygin,

Pinkas

et al. 2024

Preprint

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“…Current research has indicated that as individuals age, approximately all immune cell populations undergo changes in number and/or activity. However, these changes are typically harmful and can contribute to age-related inflammatory and tumour disease development and progression [ 28 – 32 ]. In the bladder, inflammatory and neoplastic diseases significantly increase with age[ 15 – 17 , 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Chemokine receptor 7 contributes to T- and B-cell filtering in ageing bladder, cystitis and bladder cancer

Zhao,

Luo,

Yang

et al. 2024

Immun Ageing

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Background Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported. Methods Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results. Results Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P < 0.05). Three types of T-cells (NK T-cells, γδ T-cells and naïve T-cells) and three types of B-cells (follicular B-cells, plasma and memory B-cells) were identified in aged mice bladder. Chemokine receptor 7 (CCR7) is highly expressed in aged bladder, IC/BPS and BLCA (P < 0.05). CCR7 is likely to be involved in T- and B-cell infiltration in aged bladder, IC/BPS and BLCA. Interestingly, the high CCR7 expression on BLCA cell membranes was a prognostic protective factor. Conclusions In this study, we characterised the expression profiles of immune cells in bladder tissues of aged and young mice and demonstrated that CCR7-mediated T- and B-cell filtration contributes to the development of bladder ageing, IC/BPS and BLCA.

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“…In contrast, some SASP cytokines can also attract immunosuppressive cells (e.g. myeloid-derived suppressor cells, tumor-associated macrophages, tumor-associated neutrophils, cancerassociated fibroblasts, regulatory T-cells) to suppress the senolytic effects of NK cells and T-cells [282][283][284][285]. In addition, senescent cells can upregulate immune checkpoints such as PD-L1 to attenuate T-cell responses [286,287].…”

Section: Fasni-induced Senescent Cells: An Opportunity For Immune Res...mentioning

confidence: 99%

“…In addition, senescent cells can upregulate immune checkpoints such as PD-L1 to attenuate T-cell responses [286,287]. These lines of evidence suggest that therapy-induced senescence (TIS) may be exploited as a novel immunotherapeutic strategy [224,[281][282][283][284][285][288][289][290]. If FASTIS cancer cells can stimulate the immune system to recognize and kill cancer cells, senescence induction as a mechanism of escape from FASNis could be exploited for the development of new immune response-mediated senolysis approaches.…”

Section: Fasni-induced Senescent Cells: An Opportunity For Immune Res...mentioning

confidence: 99%

Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology

Menendez,

Cuyàs,

Encinar

et al. 2024

Molecular Oncology

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The initial excitement generated more than two decades ago by the discovery of drugs targeting fatty acid synthase (FASN)‐catalyzed de novo lipogenesis for cancer therapy was short‐lived. However, the advent of the first clinical‐grade FASN inhibitor (TVB‐2640; denifanstat), which is currently being studied in various phase II trials, and the exciting advances in understanding the FASN signalome are fueling a renewed interest in FASN‐targeted strategies for the treatment and prevention of cancer. Here, we provide a detailed overview of how FASN can drive phenotypic plasticity and cell fate decisions, mitochondrial regulation of cell death, immune escape, and organ‐specific metastatic potential. We then present a variety of FASN‐targeted therapeutic approaches that address the major challenges facing FASN therapy. These include limitations of current FASN inhibitors and the lack of precision tools to maximize the therapeutic potential of FASN inhibitors in the clinic. Rethinking the role of FASN as a signal transducer in cancer pathogenesis may provide molecularly driven strategies to optimize FASN as a long‐awaited target for cancer therapeutics.

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Cellular senescence and the host immune system in aging and age-related disorders

Cited by 28 publications

References 100 publications

CD4 T Cells Acquire Cytotoxic Properties to Modulate Cellular Senescence and Aging

CD4 T Cells Acquire Cytotoxic Properties to Modulate Cellular Senescence and Aging

Chemokine receptor 7 contributes to T- and B-cell filtering in ageing bladder, cystitis and bladder cancer

Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology

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