Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions

It is widely accepted that ageing is accompanied by remodelling of the immune system, including reduced numbers of naïve T cells, increased senescent or exhausted T cells, compromise to monocyte, neutrophil and natural killer cell function and an increase in systemic inflammation. In combination these changes result in increased risk of infection, reduced immune memory, reduced immune tolerance and immune surveillance, with significant impacts upon health in old age. More recently it has become clear that the rate of decline in the immune system is malleable and can be influenced by environmental factors such as physical activity as well as pharmacological interventions. This review discusses briefly our current understanding of immunesenescence and then focuses on lifestyle interventions and therapeutic strategies that have been shown to restore immune functioning in aged individuals.

• Publication year

  2018

• Venue

  Biogerontology (Dordrecht)

• Publication date

  2018-09-29

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1007/s10522-018-9771-7PMID 30269199PMCID 6223743
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Protein Kinase A

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  2018cited by this paper
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• Statin therapy in patients with community-acquired pneumonia

  2017cited by this paper
• Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis.

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• Pulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Which Is Improved by Simvastatin

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• Fighting against a protean enemy: immunosenescence, vaccines, and healthy aging

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• Inflammaging and 'Garb-aging'.

  2017cited by this paper
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  2017cited by this paper
• Exercise-induced B cell mobilisation: Preliminary evidence for an influx of immature cells into the bloodstream.

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• Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease

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  2016cited by this paper
• Energy restriction impairs dendritic cell development in C57BL/6J mice.

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• A sestrin-dependent Erk/Jnk/p38 MAPK activation complex inhibits immunity during ageing

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• NKG2D ligands mediate immunosurveillance of senescent cells

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• Reduced levels of cytosolic DNA sensor AIM2 are associated with impaired cytokine responses in healthy elderly.

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• Aging does not affect the ability of human monocyte-derived dendritic cells to phagocytose Candida albicans

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• Shaping of NK cell subsets by aging.

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• A straight neutrophil path to healthy aging?

  2014cited by this paper
• Effect of age and CMV on NK cell subpopulations.

  2014cited by this paper
• Dysfunction of dendritic cells in aged C57BL/6 mice leads to failure of natural killer cell activation and of tumor eradication

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• Antibacterial Responses by Peritoneal Macrophages Are Enhanced Following Vitamin D Supplementation

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• Vitamin D deficiency is associated with inflammation in older Irish adults.

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  2014cited by this paper
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  2014cited by this paper
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  2013cited by this paper
• The effect of aging of the immune system on vaccination responses

  2013cited by this paper
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• A new pleiotropic effect of statins in elderly: modulation of telomerase activity

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• Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects

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• The role of nutrition in enhancing immunity in aging.

  2012influential reference
• Vaccination response following aerobic exercise: can a brisk walk enhance antibody response to pneumococcal and influenza vaccinations?

  2012cited by this paper
• Vitamin D and the immune system: new perspectives on an old theme.

  2012cited by this paper
• B cell maintenance and function in aging.

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  2012cited by this paper
• IL-7 in human health and disease.

  2012cited by this paper
• Treatment of drug-resistant tuberculosis.

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• Inflammatory markers in population studies of aging.

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  2011cited by this paper
• Age-related changes in natural killer cell receptors from childhood through old age.

  2011cited by this paper

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• Integrated analysis revealing novel associations between dietary patterns and the immune system in older adults.

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• Investigating the potential of a prematurely aged immune phenotype in severely injured patients as predictor of risk of sepsis

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• Exercise protects against cardiac and skeletal muscle dysfunction in a mouse model of inflammatory arthritis.

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• Sustaining efficient immune functions with regular physical exercise in the COVID‐19 era and beyond

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  2021cites this paper
• Helicobacter pylori Seromarkers in a University Students Population in Central Nigeria

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• Immune response to vaccination in the elderly.

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  2020cites this paper
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  2020cites this paper
• Dysregulation of leukocyte trafficking in ageing: Causal factors and possible corrective therapies.

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