Inflammation and aging: signaling pathways and intervention therapies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 8, 2023

Abstract Aging is characterized by systemic chronic inflammation, which accompanied cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there an urgent need for a systematic organization inflammaging through dimensionality reduction. Factors secreted senescent cells, known as senescence-associated secretory phenotype (SASP), promote inflammation can induce senescence in normal cells. At same time, accelerates immune resulting weakened function inability to clear cells inflammatory factors, creates vicious cycle senescence. Persistently elevated levels organs such bone marrow, liver, lungs cannot be eliminated leading damage aging-related Therefore, has been recognized endogenous factor elimination could potential strategy anti-aging. Here we discuss at molecular, cellular, organ, disease levels, review current aging models, implications cutting-edge single cell technologies, well anti-aging strategies. Since preventing alleviating diseases improving overall quality life are ultimate goals research, our highlights critical features mechanisms along with latest developments future directions providing theoretical foundation novel practical

Language: Английский

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The role of cell death in SARS-CoV-2 infection

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 20, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed disease 2019 (COVID-19). COVID-19 cases often experience distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death infected cells. Cell mechanisms have a vital role maintaining suitable environment to achieve normal functionality. Nonetheless, these processes are dysregulated, potentially contributing pathogenesis. Over the past decades, multiple pathways becoming better understood. Growing evidence suggests that induction by may significantly contributes infection pathogenicity. However, interaction SARS-CoV-2 with death, together its associated mechanisms, is yet be elucidated. In this review, we summarize existing concerning molecular modulation as well viral-host interactions, shed new light on antiviral therapy against SARS-CoV-2.

Language: Английский

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Alveolar macrophages: Achilles’ heel of SARS-CoV-2 infection

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 19, 2022

Abstract The coronavirus disease 2019 (COVID-19) pandemic has caused more than 6.3 million deaths to date. Despite great efforts curb the spread of severe acute respiratory syndrome 2 (SARS-CoV-2), vaccines and neutralizing antibodies are in gloom due persistent viral mutations antiviral compounds face challenges specificity safety. In addition, unable treat already-infected individuals, drugs cannot be used prophylactically. Therefore, exploration unconventional strategies current is highly urgent. Alveolar macrophages (AMs) residing on surface alveoli first immune cells that dispose alveoli-invading viruses. Our findings demonstrate M1 AMs have an acidic endosomal pH, thus favoring SARS-CoV-2 leave endosomes release into cytosol where virus initiates replication; contrast, M2 increased which dampens escape facilitates delivery for lysosomal degradation. this review, we propose Achilles’ heel infection modulation pH potential eliminate invaded SARS-CoV-2; same strategy might also suitable other lethal

Language: Английский

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Ferroptosis and pyroptosis signatures in critical COVID-19 patients

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(9), P. 2066 - 2077

Published: Aug. 15, 2023

Abstract Critical COVID-19 patients admitted to the intensive care unit (ICU) frequently suffer from severe multiple organ dysfunction with underlying widespread cell death. Ferroptosis and pyroptosis are two detrimental forms of regulated death that could constitute new therapeutic targets. We enrolled 120 critical in a two-center prospective cohort study monitor systemic markers ferroptosis, iron dyshomeostasis, pyroptosis, pneumocyte damage on first three consecutive days after ICU admission. Plasma 20 post-operative (PO) 39 healthy controls (HC) without failure served as controls. Subsets displayed increases individual biomarkers compared Unsupervised clustering was used discern latent clusters based biomarker profiles. Pyroptosis-related interleukin-18 accompanied by high independently associated higher odds at mechanical ventilation, while subgroup interleuking-1 beta (but limited death) reduced ventilation lower mortality hazard. Meanwhile, dyshomeostasis tendency towards ferroptosis marker malondialdehyde had no association outcome, except for small subset very catalytic survival. Forty percent did not have clear signature mechanisms studied this cohort. Moreover, repeated moderate levels soluble receptor advanced glycation end products growth differentiation factor 15 during admission adverse clinical outcome sustained levels. Altogether, data point distinct subgroups different signatures or outcomes ICU. The groups may allow ‘personalized’ treatment allocation

Language: Английский

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SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1

APOPTOSIS, Journal Year: 2023, Volume and Issue: 28(11-12), P. 1596 - 1617

Published: Sept. 2, 2023

Language: Английский

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Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(5), P. 544 - 557

Published: March 21, 2024

Abstract The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized this process might also or contribute to inflammatory disease lung failure following SARS-CoV-2 infection. To test hypothesis, developed a novel mouse-adapted model (MA20) recapitulates key pathological features of COVID-19. Concomitantly with occurrence FasL expression was significantly increased on monocytic macrophages NK cells the lungs MA20-infected mice. Importantly, therapeutic inhibition markedly survival both, young old mice coincident substantially reduced their lungs. Intriguingly, bronchoalveolar lavage fluid critically-ill patients. Together, these results identify as crucial host factor driving immuno-pathology underlies severity lethality, imply patients may benefit from FasL.

Language: Английский

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Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3246 - 3246

Published: Feb. 7, 2023

Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 potentially life-threatening contagious spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More forms of both diseases exhibit commonalities dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator function. Research advances have highlighted predictive values monocytic HLA-DR (mHLA-DR) expression for severity infectious complications patients. While regulatory mechanism altered mHLA-DR remains unclear,

Language: Английский

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Roles of p53-Mediated Host–Virus Interaction in Coronavirus Infection

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6371 - 6371

Published: March 28, 2023

The emergence of the SARS-CoV-2 coronavirus has garnered global attention due to its highly pathogenic nature and resulting health crisis economic burden. Although drugs such as Remdesivir have been considered a potential cure by targeting virus on RNA polymerase, high mutation rate unique 3' 5' exonuclease with proofreading function make it challenging develop effective anti-coronavirus drugs. As result, there is an increasing focus host-virus interactions because coronaviruses trigger stress responses, cell cycle changes, apoptosis, autophagy, dysregulation immune inflammation in host cells. p53 tumor suppressor molecule critical regulator signaling pathways, cellular DNA repair, apoptosis. However, viruses can activate or inhibit during viral infections enhance replication spread. Given pivotal role physiology, represents target for This review aims summarize relationship between from various perspectives, shed light targets antiviral drug development vaccine design.

Language: Английский

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The COVID-19 inflammation and high mortality mechanism trigger

Immunogenetics, Journal Year: 2023, Volume and Issue: 76(1), P. 15 - 25

Published: Dec. 8, 2023

Language: Английский

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The impact of ageing mechanisms on musculoskeletal system diseases in the elderly

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 7, 2024

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series physiological pathological changes. Mechanisms such as telomere depletion, stem cell macrophage dysfunction, cellular senescence gradually manifest in significantly increasing incidence diseases elderly individuals. These mechanisms interact with each other, profoundly impacting quality life older adults. As ageing population continues grow, burden on public health system expected intensify. Globally, prevalence musculoskeletal individuals increasing, resulting reduced limb mobility prolonged suffering. This review aims elucidate their interplay while exploring impact osteoarthritis, osteoporosis, sarcopenia. By delving into ageing, further research can be conducted prevent mitigate its effects, ultimate goal alleviating suffering patients future.

Language: Английский

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