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    Effects of probiotic supplementation on natural killer cell function in healthy elderly individuals: a meta-analysis of randomized controlled trials. Gui Qifeng,Wang Ange,Zhao Xinxiu,Huang Shunmei,Tan Zhongju,Xiao Chi,Yang Yunmei European journal of clinical nutrition To evaluate evidence for the role of probiotic supplementation in enhancing natural killer (NK) cell function in healthy elderly individuals. Five electronic databases were searched, and references of included articles and eligible reviews up to December 2019, with English language and human subject restrictions, were examined. Two independent reviewers identified randomized control trials (RCTs) of probiotic supplementation influencing NK cell function in healthy elderly individuals, assessed the quality of every article, and extracted data for subsequent meta-analysis. We identified six eligible trials including 364 healthy elderly subjects. Trials were heterogeneous in study design and probiotic supplementation (including genus, strain, dose, and duration). Five trials used Lactobacillus interventions alone or in combination with Bifidobacterium. Only one trial focused on Bacillus coagulans. The duration of supplementation ranged from 3 to 12 weeks, and the doses, from 1 × 10 to 4 × 10 colony-forming units. Pooling data of eligible trials showed that probiotics significantly (P < 0.05) increased NK cell activity in healthy elderly individuals (standardized mean difference = 0.777, 95% confidence interval: 0.187‒1.366, P = 0.01, I = 84.6%). Although we obtained a significant outcome, the data do not provide convincing evidence for associations between probiotic supplementation and enhancement of NK cell function, given the small final number and very large heterogeneity. More RCTs with sufficient sample sizes and long-term follow-up are needed to focus on optimal probiotic dose, species, and duration of supplementation for healthy elderly individuals. 10.1038/s41430-020-0670-z
    The role of natural killer cells in Parkinson's disease. Earls Rachael H,Lee Jae-Kyung Experimental & molecular medicine Numerous lines of evidence indicate an association between sustained inflammation and Parkinson's disease, but whether increased inflammation is a cause or consequence of Parkinson's disease remains highly contested. Extensive efforts have been made to characterize microglial function in Parkinson's disease, but the role of peripheral immune cells is less understood. Natural killer cells are innate effector lymphocytes that primarily target and kill malignant cells. Recent scientific discoveries have unveiled numerous novel functions of natural killer cells, such as resolving inflammation, forming immunological memory, and modulating antigen-presenting cell function. Furthermore, natural killer cells are capable of homing to the central nervous system in neurological disorders that exhibit exacerbated inflammation and inhibit hyperactivated microglia. Recently, a study demonstrated that natural killer cells scavenge alpha-synuclein aggregates, the primary component of Lewy bodies, and systemic depletion of natural killer cells results in exacerbated neuropathology in a mouse model of alpha-synucleinopathy, making them a highly relevant cell type in Parkinson's disease. However, the exact role of natural killer cells in Parkinson's disease remains elusive. In this review, we introduce the systemic inflammatory process seen in Parkinson's disease, with a particular focus on the direct and indirect modulatory capacity of natural killer cells in the context of Parkinson's disease. 10.1038/s12276-020-00505-7
    Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics. Bulut Ozlem,Kilic Gizem,Domínguez-Andrés Jorge Clinical reviews in allergy & immunology Non-specific innate and antigen-specific adaptive immunological memories are vital evolutionary adaptations that confer long-lasting protection against a wide range of pathogens. Adaptive memory is established by memory T and B lymphocytes following the recognition of an antigen. On the other hand, innate immune memory, also called trained immunity, is imprinted in innate cells such as macrophages and natural killer cells through epigenetic and metabolic reprogramming. However, these mechanisms of memory generation and maintenance are compromised as organisms age. Almost all immune cell types, both mature cells and their progenitors, go through age-related changes concerning numbers and functions. The aging immune system renders the elderly highly susceptible to infections and incapable of mounting a proper immune response upon vaccinations. Besides the increased infectious burden, older individuals also have heightened risks of metabolic and neurodegenerative diseases, which have an immunological component. This review discusses how immune function, particularly the establishment and maintenance of innate and adaptive immunological memory, regulates and is regulated by epigenetics, metabolic processes, gut microbiota, and the central nervous system throughout life, with a focus on old age. We explain in-depth how epigenetics and cellular metabolism impact immune cell function and contribute or resist the aging process. Microbiota is intimately linked with the immune system of the human host, and therefore, plays an important role in immunological memory during both homeostasis and aging. The brain, which is not an immune-isolated organ despite former opinion, interacts with the peripheral immune cells, and the aging of both systems influences the health of each other. With all these in mind, we aimed to present a comprehensive view of the aging immune system and its consequences, especially in terms of immunological memory. The review also details the mechanisms of promising anti-aging interventions and highlights a few, namely, caloric restriction, physical exercise, metformin, and resveratrol, that impact multiple facets of the aging process, including the regulation of innate and adaptive immune memory. We propose that understanding aging as a complex phenomenon, with the immune system at the center role interacting with all the other tissues and systems, would allow for more effective anti-aging strategies. 10.1007/s12016-021-08905-x
    Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions. Cells 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. 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. This review will focus on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging. Understanding the factors driving and enforcing NK cell aging may potentially lead to therapies countering age-related diseases and underlying drivers of the biological aging process itself. 10.3390/cells11061017