Counteracting Immunosenescence—Which Therapeutic Strategies Are Promising?

Abstract

Aging attenuates the overall responsiveness of the immune system to eradicate pathogens. The increased production of pro-inflammatory cytokines by innate immune cells under basal conditions, termed inflammaging, contributes to impaired innate immune responsiveness towards pathogen-mediated stimulation and limits antigen-presenting activity. Adaptive immune responses are attenuated as well due to lowered numbers of naïve lymphocytes and their impaired responsiveness towards antigen-specific stimulation. Additionally, the numbers of immunoregulatory cell types, comprising regulatory T cells and myeloid-derived suppressor cells, that inhibit the activity of innate and adaptive immune cells are elevated. This review aims to summarize our knowledge on the cellular and molecular causes of immunosenescence while also taking into account senescence effects that constitute immune evasion mechanisms in the case of chronic viral infections and cancer. For tumor therapy numerous nanoformulated drugs have been developed to overcome poor solubility of compounds and to enable cell-directed delivery in order to restore immune functions, e.g., by addressing dysregulated signaling pathways. Further, nanovaccines which efficiently address antigen-presenting cells to mount sustained anti-tumor immune responses have been clinically evaluated. Further, senolytics that selectively deplete senescent cells are being tested in a number of clinical trials. Here we discuss the potential use of such drugs to improve anti-aging therapy.

PD-1+ T lymphocyte proportions and hospitalized exacerbation of COPD: a prospective cohort study

“…Continuous PD-1 activation limited T cell effector function, notably cytotoxic activity. After being exposed to chronic antigens and PD-1 stimulation, T cells progressively lost effector functions, compromising infection control [32,33]. The researcher noted a significant interestingly correlation: COPD combined with anti-PD-1 or anti-PD-L1 therapy correlated with prolonged progression-free survival in lung cancer patients [13].…”

Accelerated Aging and the Life Course of Individuals Born Preterm

“…"Social health" refers to human capacities to engage in social activities and structural and functional social networks. Cross-sectional studies have identified associations between higher social health factors and cognitive activities, larger total brain volumes and hippocampal volumes, and the lower frequency of white matter hyperintensities [158], providing some support for the biological plausibility linking higher social health factors and/or cognitive activities and decreased pace of brain aging [159].…”

“…Pharmacological approaches currently under investigation include interventions to reduce chronic inflammation and metabolic dysregulation [153], strategies to enhance vaccine efficacy in the elderly [159], therapies targeting senescent cells [171], and therapies to reduce the senescence-associated secretory phenotype [172]. In mice, rapamycin, metformin, and acarbose extend lifespan [173].…”

Integrins in Health and Disease—Suitable Targets for Treatment?

“…Leukocytes are characterized by a cell-type-specific expression pattern of β 2 integrins that may be altered, for example, in response to activation [8] and aging [83]. Whereas β 2 integrins exert comparable functions in distinct cell types, like rolling on endothelial cells and phagocytosis of opsonized pathogens, they exert other functions in a more celltype-restricted manner, such as, for example, controlling reactive oxygen species (ROS) production and the release of neutrophil extracellular traps (NETs).…”