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Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions

Brauning, Ashley, Rae, Michael, Zhu, Gina, Fulton, Elena, Admasu, Tesfahun Dessale, Stolzing, Alexandra, Sharma, Amit·2022·Cells
DOI 10.3390/cells11061017PMC PMC8947539
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Abstract

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.

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  • TAC treatment concurrently induced signatures of organism growth and natural killer cell activation in PBMCs.

    “Conversely, TAC treatment concurrently induced signatures of organism growth and natural killer cell activation (Figure 3C), which are known to decline with age.25”

    From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [25]

    Section 5 reports an age-related decline in NK-cell cytotoxicity and changes in activating receptors, supporting the age-related NK-cell portion of the cited clause. Section 9 reports declining IGF-1 levels, but does not establish that an organism-growth signature declines with age. The TAC-induced PBMC signatures are presented as the citing study’s own Figure 3C result, not as a finding of this source. (LLM, conf=0.85)

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Metadata

Authors
Brauning, A., Rae, M., Zhu, G., Fulton, E., Admasu, T. D., Stolzing, A., & Sharma, A.
Affiliations
SENS Research Foundation, Mountain View, CA 94041, USA
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2022-03-17
Volume
11
Issue
6
Pages
1017
ISSN
2073-4409
DOI
10.3390/cells11061017
PMC
PMC8947539
Cited by
215
References
30
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Academy of Medicine (Healthy Longevity Catalyst Award # 2000011734.)
  • SENS Research Foundation (ApoptoSENS2019)

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