Reduced dynamic range of antiviral innate immune responses in aging

Molony, Ryan D.; Malawista, Anna; Montgomery, Ruth R.

doi:10.1016/j.exger.2017.08.019

Cited by 46 publications

(58 citation statements)

References 81 publications

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“…Whereas many immune changes have been described with aging, we will not describe in details all the aging-associated changes for each immune cell type, as this topic has been comprehensively reviewed recently ( 25 , 26 ). Collectively, the main characteristics of aging with respect to the innate system are immune stimulation at the basal level on the one hand and, immune paralysis when specific functions such as free radical production are needed, on the other hand ( 8 ).…”

Section: Immune Changes With Aging: Immunosenescence and Inflamm-aginmentioning

confidence: 99%

Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

et al. 2018

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The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro–endocrine–immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.

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Section: Immune Changes With Aging: Immunosenescence and Inflamm-aginmentioning

confidence: 99%

Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

et al. 2018

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“…To date, single cell methods have been useful in characterizing the fate of T cells [ 122 ]. Understanding the functionality and dynamics of T cell populations over prolonged periods as individuals age is especially germane [ 123 – 125 ]. Since the frequency of HIV infected cells during cART is low, functional studies of T cells infected with HIV necessitates innovative approaches that overcome technical challenges to characterizing individual infected cells.…”

Section: Dynamics Of Hiv Infected Populationsmentioning

confidence: 99%

The role of integration and clonal expansion in HIV infection: live long and prosper

Anderson¹,

Maldarelli²

2018

Retrovirology

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Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells. Cells with integrated proviruses may persist for many years, undergo clonal expansion, and produce replication competent HIV. Even proviruses with defective genomes can produce HIV RNA and may contribute to ongoing HIV pathogenesis. New analyses of HIV infected cells suggest that over time on cART, there is a shift in the composition of the population of HIV infected cells, with the infected cells that persist over prolonged periods having proviruses integrated in genes associated with regulation of cell growth. In several cases, strong evidence indicates the presence of the provirus in specific genes may determine persistence, proliferation, or both. These data have raised the intriguing possibility that after cART is introduced, a selection process enriches for cells with proviruses integrated in genes associated with cell growth regulation. The dynamic nature of populations of cells infected with HIV during cART is not well understood, but is likely to have a profound influence on the composition of the HIV reservoir with critical consequences for HIV eradication and control strategies. As such, integration studies will shed light on understanding viral persistence and inform eradication and control strategies. Here we review the process of HIV integration, the role that integration plays in persistence, clonal expansion of the HIV reservoir, and highlight current challenges and outstanding questions for future research.

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“…Over the past 250 years life expectancy has increased dramatically and is still increasing at 2 years per decade in most countries. Advancing age is accompanied by a compromised ability of older adults to combat bacterial and viral infections (Gavazzi and Krause 2002 ; Molony et al 2017a , b ), increased risk of autoimmunity (Goronzy and Weyand 2012 ), poor vaccination responses (Del Giudice et al 2017 ; Lord 2013 ) and the re-emergence of latent infections to produce conditions such as shingles (Schmader 2001 ). All of this contributing towards increased morbidity and mortality in older adults (Pera et al 2015 ) and indicative of reduced immunity.…”

Section: Immune Ageing and Healthmentioning

confidence: 99%

Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions

Duggal

2018

Biogerontology

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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.

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Reduced dynamic range of antiviral innate immune responses in aging

Cited by 46 publications

References 81 publications

Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

The role of integration and clonal expansion in HIV infection: live long and prosper

Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions

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