Long-term human spaceflight and inflammaging: Does it promote aging?

Capri, Miriam; Conte, Maria; Ciurca, Erika; Pirazzini, Chiara; Garagnani, Paolo; Santoro, Aurelia; Longo, Federica; Salvioli, Stefano; Lau, Patrick; Moeller, Ralf; Jordan, J. Scott; Illig, Thomas; Villanueva, Maria-Moreno; Grüber, Markus; Bürkle, Alexander; Franceschi, Claudio; Rittweger, Jörn

doi:10.1016/j.arr.2023.101909

Cited by 23 publications

(12 citation statements)

References 221 publications

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“…5 ). While our results show a decrease in most DC secreted cytokines upon exposure to RPM conditioning as well as a looser tissue niche, both of which simulate “aged” conditions, studies of cytokine levels in astronauts’ blood has shown dysregulation in certain cytokines, such as an increase in TNFα, IL-10, and IL-6 levels, during spaceflight 60 – 63 . These differences could be due to the fact that our system isolates and focuses on only DC differentiation and function.…”

Section: Discussionmentioning

confidence: 53%

Effects of an aged tissue niche on the immune potency of dendritic cells using simulated microgravity

et al. 2023

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Microgravity accelerates the aging of various physiological systems, and it is well acknowledged that aged individuals and astronauts both have increased susceptibility to infections and poor response to vaccination. Immunologically, dendritic cells (DCs) are the key players in linking innate and adaptive immune responses. Their distinct and optimized differentiation and maturation phases play a critical role in presenting antigens and mounting effective lymphocyte responses for long-term immunity. Despite their importance, no studies to date have effectively investigated the effects of microgravity on DCs in their native microenvironment, which is primarily located within tissues. Here, we address a significantly outstanding research gap by examining the effects of simulated microgravity via a random positioning machine on both immature and mature DCs cultured in biomimetic collagen hydrogels, a surrogate for tissue matrices. Furthermore, we explored the effects of loose and dense tissues via differences in collagen concentration. Under these various environmental conditions, the DC phenotype was characterized using surface markers, cytokines, function, and transcriptomic profiles. Our data indicate that aged or loose tissue and exposure to RPM-induced simulated microgravity both independently alter the immunogenicity of immature and mature DCs. Interestingly, cells cultured in denser matrices experience fewer effects of simulated microgravity at the transcriptome level. Our findings are a step forward to better facilitate healthier future space travel and enhance our understanding of the aging immune system on Earth.

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Section: Discussionmentioning

confidence: 53%

Effects of an aged tissue niche on the immune potency of dendritic cells using simulated microgravity

et al. 2023

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“…However, as astronauts venture further into space, the dose rate will increase to 110-300 mSv/year on the Moon and 130-260 mSv/year on Mars. Since solid tumor induction may occur at effective doses as low as 200 mSv (20) and radiation health effects for astronauts include but are not limited to accelerated aging of tissues, an increased risk of cardiovascular disease, cancer, and neurodegeneration (21,22), radiation countermeasures are needed to protect astronauts.…”

Section: Session I: Microphysiological Systems and Chip Technologiesmentioning

confidence: 99%

Advanced Technologies in Radiation Research

Rios,

DiCarlo,

Harrison

et al. 2024

Radiation Research

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The U.S. Government is committed to maintaining a robust research program that supports a portfolio of scientific experts who are investigating the biological effects of radiation exposure. On August 17 and 18, 2023, the Radiation and Nuclear Countermeasures Program, within the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), partnered with the National Cancer Institute, NIH, the National Aeronautics and Space Administration, and the Radiation Injury Treatment Network to convene a workshop titled, Advanced Technologies in Radiation Research (ATRR), which focused on the use of advanced technologies under development or in current use to accelerate radiation research. This meeting report provides a comprehensive overview of the research presented at the workshop, which included an assembly of subject matter experts from government, industry, and academia. Topics discussed during the workshop included assessments of acute and delayed effects of radiation exposure using modalities such as clustered regularly interspaced short palindromic repeats (CRISPR) – based gene editing, tissue chips, advanced computing, artificial intelligence, and immersive imaging techniques. These approaches are being applied to develop products to diagnose and treat radiation injury to the bone marrow, skin, lung, and gastrointestinal tract, among other tissues. The overarching goal of the workshop was to provide an opportunity for the radiation research community to come together to assess the technological landscape through sharing of data, methodologies, and challenges, followed by a guided discussion with all participants. Ultimately, the organizers hope that the radiation research community will benefit from the workshop and seek solutions to scientific questions that remain unaddressed. Understanding existing research gaps and harnessing new or re-imagined tools and methods will allow for the design of studies to advance medical products along the critical path to U.S. Food and Drug Administration approval.

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“…We also did not discuss other potential applications of PPSS. Recent reviews on spaceflight, microgravity, and simulated microgravity have shown that multiple organ systems are involved in the response of the organism to these stressors [115][116][117][118][119][120]. The response to these stressors converges on the inflammatory response, which is a driver of aging [117].…”

Section: Limitationsmentioning

confidence: 99%

“…Recent reviews on spaceflight, microgravity, and simulated microgravity have shown that multiple organ systems are involved in the response of the organism to these stressors [115][116][117][118][119][120]. The response to these stressors converges on the inflammatory response, which is a driver of aging [117]. Countermeasures for spaceflight and microgravity in the form of active pulsatile shear stress (aerobic exercise) have been reviewed by others [121][122][123][124].…”

Section: Limitationsmentioning

confidence: 99%

Harnessing Passive Pulsatile Shear Stress for Alzheimer’s Disease Prevention and Intervention

Adams,

Uryash,

Lopez

2024

JAD

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Alzheimer’s disease (AD) affects more than 40 million people worldwide and is the leading cause of dementia. This disease is a challenge for both patients and caregivers and puts a significant strain on the global healthcare system. To address this issue, the Lancet Commission recommends focusing on reducing modifiable lifestyle risk factors such as hypertension, diabetes, and physical inactivity. Passive pulsatile shear stress (PPSS) interventions, which use devices like whole-body periodic acceleration, periodic acceleration along the Z-axis (pGz), and the Jogging Device, have shown significant systemic and cellular effects in preclinical and clinical models which address these modifiable risks factors. Based on this, we propose that PPSS could be a potential non-pharmacological and non-invasive preventive or therapeutic strategy for AD. We perform a comprehensive review of the biological basis based on all publications of PPSS using these devices and demonstrate their effects on the various aspects of AD. We draw from this comprehensive analysis to support our hypothesis. We then delve into the possible application of PPSS as an innovative intervention. We discuss how PPSS holds promise in ameliorating hypertension and diabetes while mitigating physical inactivity, potentially offering a holistic approach to AD prevention and management.

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Long-term human spaceflight and inflammaging: Does it promote aging?

Cited by 23 publications

References 221 publications

Effects of an aged tissue niche on the immune potency of dendritic cells using simulated microgravity

Effects of an aged tissue niche on the immune potency of dendritic cells using simulated microgravity

Advanced Technologies in Radiation Research

Harnessing Passive Pulsatile Shear Stress for Alzheimer’s Disease Prevention and Intervention

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