Immunological outcomes of exercise in older adults

Aging is associated with a dysregulation of the immune system known as immunosenescence. Immunosenescence involves cellular and molecular alterations that impact both innate and adaptive immunity, leading to increased incidences of infectious disease morbidity and mortality as well as heightened rates of other immune disorders such as autoimmunity, cancer, and inflammatory conditions. While current data suggests physical activity may be an effective and logistically easy strategy for counteracting immunosenescence, it is currently underutilized in clinical settings. Long-term, moderate physical activity interventions in geriatric populations appear to be associated with several benefits including reduction in infectious disease risk, increased rates of vaccine efficacy, and improvements in both physical and psychosocial aspects of daily living. Exercise may also represent a viable therapy in patients for whom pharmacological treatment is unavailable, ineffective, or inappropriate. The effects of exercise impact multiple aspects of immune response including T cell phenotype and proliferation, antibody response to vaccination, and cytokine production. However, an underlying mechanism by which exercise affects numerous cell types and responses remains to be identified. Given this evidence, an increase in the use of physical activity programs by the healthcare community may result in improved health of geriatric populations

Peripheral inflammatory cytokines and motor symptoms in persons with Parkinson's disease

Background Many of the motor symptoms of Parkinson's disease (PD) impact quality of life and are not fully ameliorated by current pharmacological and surgical treatments. A better understanding of the pathophysiology underlying these symptoms is needed. Previous research has suggested that inflammation may play a significant role in PD pathophysiology and progression, but there is limited research exploring how inflammation directly relates to motor symptoms in PD. Thus, the purpose of this study was to evaluate associations between peripheral immune inflammatory markers and motor symptoms of PD, specifically, tremor, bradykinesia, and postural and gait instability. We hypothesized that peripheral inflammatory cytokines would predict the severity of motor symptoms in persons with PD, and that there will be higher levels of peripheral inflammatory cytokine markers in persons with PD when compared to age-matched healthy older adults. Methods Twenty-six participants with PD and fourteen healthy older adults completed the study. For participants with PD, the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) was recorded and scored by two Movement Disorders Neurologists masked to the study. A blood sample was collected from both participants with PD and the healthy older adults. Through the MILLIPLEX® map High Sensitivity Human Cytokine Kit, key inflammation-related markers were analyzed (TNF-α, IFN-γ, IL-1β, IL-8, IL-2, IL-7, IL-5, IL-13, IL, 4, IL-10 IL-12p70, GM-CSF, and IL-6). Results Results revealed significantly higher levels of IL-6 in persons with PD when compared to healthy older adults (p ​= ​0.005). Moreover, results revealed that higher levels of IL-4 (p ​= ​0.011) and lower levels of IFNγ (p ​= ​0.003) significantly predicted more severe tremor in persons with PD. No other associations between the peripheral inflammation markers and other motor symptoms were observed. Conclusions Overall, these results are consistent with a growing body of literature that implicates inflammatory cytokines in the PD, and further suggests that inflammatory cytokines, or lack thereof, may be associated with tremor in persons with PD. Keywords: Parkinson's diseasePeripheral inflammationInflammatory cytokinesMotor impairmentsMovement Disorders Society Unified Parkinson's Disease Rating ScaleThis article is published as Diaz, K., Kohut, M.L., Russell, D.W., Stegemoller, E.L., Peripheral inflammatory cytokines and motor symptoms in persons with Parkinson's disease. Brain, Behavior, Immunity Healthy, May 2022, 21(100442); https://doi.org/10.1016/j.bbih.2022.100442 Posted with permission

“Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation

The loss in age-related immunological markers, known as immunosenescence, is caused by a combination of factors, one of which is inflammaging. Inflammaging is associated with the continuous basal generation of proinflammatory cytokines. Studies have demonstrated that inflammaging reduces the effectiveness of vaccines. Strategies aimed at modifying baseline inflammation are being developed to improve vaccination responses in older adults. Dendritic cells have attracted attention as an age-specific target because of their significance in immunization as antigen presenting cells that stimulate T lymphocytes.This article is published as Ananya, Ananya, Kaitlyn G. Holden, Zhiling Gu, Dan Nettleton, Surya K. Mallapragada, Michael J. Wannemuehler, Marian L. Kohut, and Balaji Narasimhan. “Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation. Immunity & Ageing 20, no. 1 (2023): 1-16. DOI: 10.1186/s12979-023-00332-0. Copyright 2023 The Author(s). Attribution 4.0 International (CC BY 4.0). Posted with permission

Endocrine Responses to Chronic Androstenedione Intake in 30- to 56-Year-Old Men

In young men, chronic ingestion of 100 mg androstenedione (ASD), three times per day, does not increase serum total testosterone but does increase serum estrogen and ASD concentrations. We investigated the effects of ASD ingestion in healthy 30- to 56-yr-old men. In a double-blind, randomly assigned manner, subjects consumed 100 mg ASD three times daily (n = 28), or placebo (n = 27) for 28 days. Serum ASD , dihydrotestosterone (DHT), free and total testosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured at week 0 and each week throughout the supplementation period. Serum total testosterone and PSA concentrations did not change with supplementation. Elevated serum concentrations of ASD (300%), free testosterone (45%), DHT (83%), and estradiol (68%) were observed during weeks 1–4 in ASD (P \u3c 0.05). There was no relationship between age and changes in serum ASD (r2 = 0.024), free testosterone (r2 = 0.00), or estradiol (r2 = 0.029) concentrations with ASD, whereas the serum DHT response to ASD ingestion was related to age (r2 = 0.244; P \u3c 0.05). Serum concentrations of high-density lipoprotein cholesterol were decreased by 10% during the supplementation period (P \u3c 0.05). These results suggest that the ingestion of 100 mg ASD , three times per day, does not increase serum total testosterone or PSA concentrations but does elicit increases in ASD, free testosterone, estradiol, and DHT and decreases serum high-density lipoprotein cholesterol concentrations

Novel nanoadjuvants balance immune activation with modest inflammation: implications for older adult vaccines

Background Age-associated impairments of immune response and inflammaging likely contribute to poor vaccine efficacy. An appropriate balance between activation of immune memory and inflammatory response may be more effective in vaccines for older adults; attempts to overcome reduced efficacy have included the addition of adjuvants or increased antigenic dose. Next generation vaccine formulations may also use biomaterials to both deliver and adjuvant vaccine antigens. In the context of aging, it is important to determine the degree to which new biomaterials may enhance antigen-presenting cell (APC) functions without inducing potent inflammatory responses of APCs or other immune cell types (e.g., T cells). However, the effect of newer biomaterials on these cell types from young and older adults remains unknown. Results In this pilot study, cells from young and older adults were used to evaluate the effect of novel biomaterials such as polyanhydride nanoparticles (NP) and pentablock copolymer micelles (Mi) and cyclic dinucleotides (CDN; a STING agonist) on cytokine and chemokine secretion in comparison to standard immune activators such as lipopolysaccharide (LPS) and PMA/ionomycin. The NP treatment showed adjuvant-like activity with induction of inflammatory cytokines, growth factors, and select chemokines in peripheral blood mononuclear cells (PBMCs) of both young (n = 6) and older adults (n = 4), yet the degree of activation was generally less than LPS. Treatment with Mi or CDN resulted in minimal induction of cytokines and chemokine secretion with the exception of increased IFN-α and IL-12p70 by CDN. Age-related decreases were observed across multiple cytokines and chemokines, yet IFN-α, IL-12, and IL-7 production by NP or CDN stimulation was equal to or greater than in cells from younger adults. Consistent with these results in aged humans, a combination nanovaccine composed of NP, Mi, and CDN administered to aged mice resulted in a greater percentage of antigen-specific CD4+ T cells and greater effector memory cells in draining lymph nodes compared to an imiquimod-adjuvanted vaccine. Conclusions Overall, our novel biomaterials demonstrated a modest induction of cytokine secretion with a minimal inflammatory profile. These findings suggest a unique role for biomaterial nanoadjuvants in the development of next generation vaccines for older adults.This article is published as Ross, K.A., Tingle, A.M., Senapati, S. et al. Novel nanoadjuvants balance immune activation with modest inflammation: implications for older adult vaccines. Immun Ageing 20, 28 (2023). https://doi.org/10.1186/s12979-023-00349-5. © The Author(s) 2023.This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data

Novel nanoadjuvants balance immune activation with modest inflammation: implications for older adult vaccines

Abstract Background Age-associated impairments of immune response and inflammaging likely contribute to poor vaccine efficacy. An appropriate balance between activation of immune memory and inflammatory response may be more effective in vaccines for older adults; attempts to overcome reduced efficacy have included the addition of adjuvants or increased antigenic dose. Next generation vaccine formulations may also use biomaterials to both deliver and adjuvant vaccine antigens. In the context of aging, it is important to determine the degree to which new biomaterials may enhance antigen-presenting cell (APC) functions without inducing potent inflammatory responses of APCs or other immune cell types (e.g., T cells). However, the effect of newer biomaterials on these cell types from young and older adults remains unknown. Results In this pilot study, cells from young and older adults were used to evaluate the effect of novel biomaterials such as polyanhydride nanoparticles (NP) and pentablock copolymer micelles (Mi) and cyclic dinucleotides (CDN; a STING agonist) on cytokine and chemokine secretion in comparison to standard immune activators such as lipopolysaccharide (LPS) and PMA/ionomycin. The NP treatment showed adjuvant-like activity with induction of inflammatory cytokines, growth factors, and select chemokines in peripheral blood mononuclear cells (PBMCs) of both young (n = 6) and older adults (n = 4), yet the degree of activation was generally less than LPS. Treatment with Mi or CDN resulted in minimal induction of cytokines and chemokine secretion with the exception of increased IFN-α and IL-12p70 by CDN. Age-related decreases were observed across multiple cytokines and chemokines, yet IFN-α, IL-12, and IL-7 production by NP or CDN stimulation was equal to or greater than in cells from younger adults. Consistent with these results in aged humans, a combination nanovaccine composed of NP, Mi, and CDN administered to aged mice resulted in a greater percentage of antigen-specific CD4+ T cells and greater effector memory cells in draining lymph nodes compared to an imiquimod-adjuvanted vaccine. Conclusions Overall, our novel biomaterials demonstrated a modest induction of cytokine secretion with a minimal inflammatory profile. These findings suggest a unique role for biomaterial nanoadjuvants in the development of next generation vaccines for older adults

Schematic diagram for the proposed underlying mechanism.

<p>SOCS3 was a negative regulator that undermines innate immunity against influenza virus infection. <i>H. perforatum</i> extract elevated SOCS3, and thus impaired the required anti-viral immune defense system, resulting in uncontrolled infection and sustained inflammation.</p