Senescent cell clearance by the immune system

Emerging therapeutic opportunities

Larissa G.P.Langhi Prata, Inna G. Ovsyannikova, Tamara Tchkonia, James L Kirkland

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Senescent cells (SCs)arise from normal cells in multiple organs due to inflammatory, metabolic, DNA damage, or tissue damage signals. SCs are non-proliferating but metabolically active cells that can secrete a range of pro-inflammatory and proteolytic factors as part of the senescence-associated secretory phenotype (SASP). Senescent cell anti-apoptotic pathways (SCAPs)protect SCs from their own pro-apoptotic SASP. SCs can chemo-attract immune cells and are usually cleared by these immune cells. During aging and in multiple chronic diseases, SCs can accumulate in dysfunctional tissues. SCs can impede innate and adaptive immune responses. Whether immune system loss of capacity to clear SCs promotes immune system dysfunction, or conversely whether immune dysfunction permits SC accumulation, are important issues that are not yet fully resolved. SCs may be able to assume distinct states that interact differentially with immune cells, thereby promoting or inhibiting SC clearance, establishing a chronically pro-senescent and pro-inflammatory environment, leading to modulation of the SASP by the immune cells recruited and activated by the SASP. Therapies that enhance immune cell-mediated clearance of SCs could provide a lever for reducing SC burden. Such therapies could include vaccines, small molecule immunomodulators, or other approaches. Senolytics, drugs that selectively eliminate SCs by transiently disabling their SCAPs, may prove to alleviate immune dysfunction in older individuals and thereby accelerate immune-mediated clearance of SCs. The more that can be understood about the interplay between SCs and the immune system, the faster new interventions may be developed to delay, prevent, or treat age-related dysfunction and the multiple senescence-associated chronic diseases and disorders.

Original languageEnglish (US)
JournalSeminars in immunology
DOIs
StatePublished - Jan 1 2019

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Immune System
Therapeutics
Phenotype
Immunologic Factors
Adaptive Immunity

Keywords

  • Chemokines
  • Cytokines
  • Immune system
  • Senescent cells
  • Senolytics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Senescent cell clearance by the immune system : Emerging therapeutic opportunities. / Prata, Larissa G.P.Langhi; Ovsyannikova, Inna G.; Tchkonia, Tamara; Kirkland, James L.

In: Seminars in immunology, 01.01.2019.

Research output: Contribution to journalReview article

Prata, Larissa G.P.Langhi ; Ovsyannikova, Inna G. ; Tchkonia, Tamara ; Kirkland, James L. / Senescent cell clearance by the immune system : Emerging therapeutic opportunities. In: Seminars in immunology. 2019.
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abstract = "Senescent cells (SCs)arise from normal cells in multiple organs due to inflammatory, metabolic, DNA damage, or tissue damage signals. SCs are non-proliferating but metabolically active cells that can secrete a range of pro-inflammatory and proteolytic factors as part of the senescence-associated secretory phenotype (SASP). Senescent cell anti-apoptotic pathways (SCAPs)protect SCs from their own pro-apoptotic SASP. SCs can chemo-attract immune cells and are usually cleared by these immune cells. During aging and in multiple chronic diseases, SCs can accumulate in dysfunctional tissues. SCs can impede innate and adaptive immune responses. Whether immune system loss of capacity to clear SCs promotes immune system dysfunction, or conversely whether immune dysfunction permits SC accumulation, are important issues that are not yet fully resolved. SCs may be able to assume distinct states that interact differentially with immune cells, thereby promoting or inhibiting SC clearance, establishing a chronically pro-senescent and pro-inflammatory environment, leading to modulation of the SASP by the immune cells recruited and activated by the SASP. Therapies that enhance immune cell-mediated clearance of SCs could provide a lever for reducing SC burden. Such therapies could include vaccines, small molecule immunomodulators, or other approaches. Senolytics, drugs that selectively eliminate SCs by transiently disabling their SCAPs, may prove to alleviate immune dysfunction in older individuals and thereby accelerate immune-mediated clearance of SCs. The more that can be understood about the interplay between SCs and the immune system, the faster new interventions may be developed to delay, prevent, or treat age-related dysfunction and the multiple senescence-associated chronic diseases and disorders.",
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