A New Look At L. Reuteri And Why It Had a Rejuvenating Effect

[OtyMac]

This post explains many aspects of the study but I want to add a different angle to what I think could be going on.

https://www.gourmetstylewellness.com/interact/threads/atcc-pta-6475-the-cure-we-arent-talking-about.116347/

It is well established that senolytics have a rejuvenating effect and life extension properties. If I remember correctly, only about 20% of senescent cells can be removed by senolytic compounds.

The body has a much better way by using its own senolytic disposal mechanism thru natural killer cells and T-cells. The problem is the immune system we need to remove senescent cells(in the scalp and elsewhere) are also under the process of becoming senescent in themselves.

L. Reuteri and other probiotics are known to increase T-cell function. So we have a plausible mechanism(I think) for the L. Reuteri rejuvenation effect and that is increasing immune function which remove senescent cells.

Activation of Natural Killer Cells by Probiotics - PMC

During the last decade, probiotics have been established to be important mediators of host immunity. Their effects on both innate and adaptive immunity have been documented in the literature. Although several reports have correlated different ...

pmc.ncbi.nlm.nih.gov

In addition, L. reuteri has stimulatory effects on the immune system by increasing T cell development and function [15]. Upon supplementation with L. reuteri ATCC 55730, B lymphocyte numbers were increased and promoted increased numbers of CD4-positive T-lymphocytes in the ileal epithelium [18]. There is growing interest in the immune-boosting potential of L. reuteri; however, its efficacy is limited to certain strains.

 

[OtyMac]

The IL-17 inhibitor study is interesting too because not only did the guy regrow a decent amount of hair, the color changed from gray to black. It looks like his skin tone is different color and less saggy on his chest too. So...there was IMO some rejuvenation going on other than just his scalp.

https://www.gourmetstylewellness.com/interact/threads/repigmentation-and-new-growth-of-hairs-after-anti-interleukin-17-therapy-with-secukinumab.114788/

It looks like IL-17 inhibitors have a positive effect on NK cell activity which could reduce senescent cell populations.
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Interleukin-17 (IL-17) can limit the activity of natural killer (NK) cells, but IL-17 inhibitors may help improve NK cell function.



How IL-17 affects NK cells

• IL-17 can reduce NK cell maturation, which can limit their ability to fight tumors and viruses.
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• IL-17 can make NK cells less responsive to IL-15, which is important for NK cell maturation.
  
  
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• IL-17 signaling can activate cytolytic NK cells in response to placental ischemia.
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  Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions - PMC

  Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer’s and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one ...

  pmc.ncbi.nlm.nih.gov
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• Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer’s and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one important cause of age-related morbidity and mortality, which may extend beyond its role in infectious disease. One aspect of immunosenescence that has received less attention is age-related natural killer (NK) cell dysfunction, characterized by reduced cytokine secretion and decreased target cell cytotoxicity, accompanied by and despite an increase in NK cell numbers with age.
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• Moreover, recent studies have revealed that NK cells are the central actors in the immunosurveillance of senescent cells, whose age-related accumulation is itself a probable contributor to the chronic sterile low-grade inflammation developed with aging (“inflammaging”). NK cell dysfunction is therefore implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age

 

[OtyMac]

High dose androgen suppresses natural killer cytotoxicity of castration-resistant prostate cancer cells via altering AR/circFKBP5/miRNA-513a-5p/PD-L1 signals - PMC

Most advanced prostate cancer (PCa) patients initially respond well to androgen deprivation therapy, but almost all eventually develop castration-resistant prostate cancer (CRPC). Early studies indicated the bipolar androgen therapy via a cycling of ...

pmc.ncbi.nlm.nih.gov

A high dose DHT through AR can suppress the cytotoxicity of NK cells to kill CRPC cells​

EnzS1-C4-2 and EnzR1-C4-2 cells were treated with different doses of DHT (1 nM, 10 nM and 50 nM) for 48 h. Results from the MTT assay (detailed procedure described in Fig. 1A) showed that adding NK cells with multiple E:T ratios (1:1, 2:1 and 5:1) to high dose DHT (50 nM)-treated CRPC cells resulted in impaired killing efficacy of NK cells (Fig. 1B). To directly measure the leakiness of plasma membrane caused by the pore forming cytolytic perforin and granzymes from the NK cells, we measured the lactate dehydrogenase activity in the media after NK cell co-culture (detailed procedure described in Fig. 1A). The results revealed that adding NK cells to these 50 nM DHT-treated CRPC cells resulted in reduced efficacy of NK cytotoxicity (Fig. 1C). These complementing results indicated that a high dose DHT could reduce the immunological efficacy of NK cells towards CRPC cells. In comparison, NK cytotoxicity was not weakened by treatment with lower doses (1 nM and 10 nM) of DHT (Fig. 1B, C).

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[OtyMac]

Senescence appears to drive both male pattern baldness and BPH.

The Senescence-Associated Secretory Phenotype Promotes Benign Prostatic Hyperplasia - PMC

Benign prostatic hyperplasia (BPH) is characterized by increased tissue mass in the transition zone of the prostate, which leads to obstruction of urine outflow and considerable morbidity in a majority of older men. Senescent cells accumulate in ...

pmc.ncbi.nlm.nih.gov

In summary, both correlative and functional evidence support the hypothesis that the senescence-associated secretory phenotype can promote the development of BPH, which is the single most common age-related pathology in older men.

 

[OtyMac]

Vitamin D Enhances Immune Effector Pathways of NK Cells Thus Providing a Mechanistic Explanation for the Increased Effectiveness of Therapeutic Monoclonal Antibodies - PMC

Patients with diffuse large cell lymphoma who have an adequate vitamin D supply derive significantly more benefit from immuno-chemotherapy with rituximab than patients with vitamin D deficiency; this is especially true for female patients. We have ...

pmc.ncbi.nlm.nih.gov

We could show that the “NK cell-associated cytotoxicity pathway” from the KEGG database among other Interferon-related pathways was significantly upregulated after vitamin D substitution. This is mainly caused by upregulated IFN-α genes (IFN2, -4, -6, -7, and -10) and this finding is in line with the expectation we had from our clinical [12] and translational [14] results of vitamin D activity and NK-cell-mediated ADCC. Also, IFNL3 was shown to be upregulated. We, therefore, propose that increased interferon production plays the most important role in vitamin D enhancement of NK cell activity.

 

[OtyMac]

IL-17 constrains natural killer cell activity by restraining IL-15-driven cell maturation via SOCS3 - PubMed

Increasing evidence demonstrates that IL-17A promotes tumorigenesis, metastasis, and viral infection. Natural killer (NK) cells are critical for defending against tumors and infections. However, the roles and mechanisms of IL-17A in regulating NK cell activity remain elusive. Herein, our study...

pubmed.ncbi.nlm.nih.gov

Increasing evidence demonstrates that IL-17A promotes tumorigenesis, metastasis, and viral infection. Natural killer (NK) cells are critical for defending against tumors and infections. However, the roles and mechanisms of IL-17A in regulating NK cell activity remain elusive.

Herein, our study demonstrated that IL-17A constrained NK cell antitumor and antiviral activity by restraining NK cell maturation. It was observed that the development and metastasis of tumors were suppressed in IL-17A-deficient mice in the NK cell-dependent manner.

In addition, the antiviral activity of NK cells was also improved in IL-17A-deficient mice.

 

[OtyMac]

Recent insights into the crosstalk between senescent cells and CD8 T lymphocytes - npj Aging

Recent reports in oncological and non-oncological experimental setups provide strong evidence that senescent cells are under the surveillance of CD8 T cell-mediated adaptive immunity. These new data also shed light on the mechanisms that sensitize senescent cells to CD8 T cell-dependent killing...

www.nature.com

Recent reports in oncological and non-oncological experimental setups provide strong evidence that senescent cells are under the surveillance of CD8 T cell-mediated adaptive immunity. These new data also shed light on the mechanisms that sensitize senescent cells to CD8 T cell-dependent killing, as well as those that enable senescent cells to evade CD8 T cell immunosurveillance. Understanding the interplay between cellular senescence and the adaptive immune system may open new strategies to ameliorate aging and aging-associated diseases.

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Repurposing nitric oxide donating drugs in cancer therapy through immune modulation - Journal of Experimental & Clinical Cancer Research

Background Nitric oxide-releasing drugs are used for cardiovascular diseases; however, their effects on the tumor immune microenvironment are less clear. Therefore, this study explored the impact of nitric oxide donors on tumor progression in immune-competent mice. Methods The effects of three...

jeccr.biomedcentral.com

Nitric oxide donors increased the number of CD8+ T cells with activation gene signatures, as indicated by single-cell RNA sequencing. Flow cytometry analysis confirmed an increase in infiltrating CD8+ T cells and dendritic cells.

The antitumor effect of nitric oxide donors was abolished by depletion of CD8+ T cells, indicating the requirement for CD8+ T cells. Tumor inhibition correlated with a decrease in a subtype of protumor macrophages and an increase in a subset of Arg1-positive macrophages expressing antitumor gene signatures. The increase in this subset of macrophages was confirmed by flow cytometry analysis. Finally, the combination of low-dose nitric oxide donor and cisplatin induced an additive cancer therapeutic effect in two immunocompetent animal models. The enhanced therapeutic effect was accompanied by an increase in the cells expressing the gene signature of NK cell.

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https://www.pnas.org/doi/10.1073/pnas.0607873103

Treatment with l-arginine or l-citrulline of eNOS-transfected cells partially inhibited, and combination of l-arginine and l-citrulline with antioxidants strongly prevented, high glucose-induced cellular senescence. These data demonstrate that NO can prevent endothelial senescence, thereby contributing to the anti-senile action of estrogen. The ingestion of NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can delay endothelial senescence under high glucose.