[Phospho-aging/MHU-6]
Mechanism of accelerated aging under microgravity

RESEARCH OVERVIEW

• Under microgravity conditions, aging-like symptoms such as bone loss and muscle atrophy appear rapidly in both mice and astronauts, but the molecular mechanism behind the ‘accelerated aging’ in space remains elusive. Based on the analysis using a mouse model of human premature-aging syndromes, it has been identified that colloidal nanoparticles composed of calcium-phosphate precipitates, named CPPs, are a pro-aging factor in mammals. The Mechanism of Accelerated Aging under Microgravity (Mouse Habitat Unit-6 or MHU-6) investigation focuses on the molecular mechanism behind the ‘accelerated aging’ in space in terms of CPPs identified as a pro-aging factor in mammals.
• When bone and muscle mass rapidly decrease under microgravity conditions, a considerable amount of phosphate stored in bone and muscle should flow into the blood. Thus, it is hypothesized that the mechanism by which microgravity induces accelerated aging symptoms may be identical with the mechanism by which phosphate overload accelerates aging. The aim of MHU-6 is to verify this hypothesis using mice housed under microgravity. Specifically, mice are sent into space, where blood and tissues samples are obtained for comparison with those obtained from the age- and sex-matched mice housed on the ground.
• MHU-6 seeks to provide scientific evidence showing that osteoporosis and osteopenia are not merely results of aging, but also causes of aging. Therapeutic interventions to prevent loss of bone and muscle as a practical anti-aging countermeasure may contribute to extension of a healthy life span in humans.

DESCRIPTION

Under microgravity conditions, aging-like symptoms such as loss of bone and muscle appear rapidly in mice and astronauts. However, the molecular mechanism behind the ‘accelerated aging’ in space remains elusive. Based on the analysis of a mouse model of human premature aging syndromes, it has been identified that CPPs are a pro-aging factor in mammals. CPPs are colloidal nanoparticles composed of calcium-phosphate precipitates and serum proteins. CPPs are dispersed in the blood and urine and increase upon phosphate overload (i.e., increase in dietary phosphate intake and/or decrease in the ability to excrete phosphate into urine). It has been found that CPPs behave like a pathogen that induces inflammatory responses and arteriosclerosis in the blood, or renal tubular damage and fibrosis in the urine - thus proposing a “CPP theory of aging”. Namely, chronic inflammation and systemic tissue damages induced by CPPs may accelerate aging.

When the bone and muscle are rapidly decreased under microgravity conditions, a considerable amount of phosphate stored in the bone and muscle should flow into the blood. Thus, it is hypothesized that the mechanism by which microgravity accelerates aging may be identical with the mechanism by which phosphate overload accelerates aging. The aim of Mechanism of Accelerated Aging Under Microgravity (Mouse Habitat Unit-6 or MHU-6) is to test this hypothesis in mice. Specifically, mice are sent into space where blood and tissue samples are collected and compared with those obtained from the age- and sex-matched mice kept on the ground. The research team can determine whether microgravity may increase CPPs and induce pathological conditions resembling those induced by phosphate overload, such as inflammation and kidney damages. The team also uses an unbiased approach that utilizes various ‘omics’ techniques to build a new hypothesis in case the CPP theory of aging is disproved. If successful, scientific evidence can be provided showing that osteoporosis and osteopenia are not merely results of aging, but also causes of aging - justifying therapeutic interventions to prevent loss of bone and muscle as a practical anti-aging medicine that may contribute to extension of health span in humans.

SPACE APPLICATIONS

Bone and muscle loss on long-duration missions poses a significant risk to astronaut health. A better understanding of the mechanism behind this loss could lead to improved countermeasures and treatments to protect crews on future missions.

EARTH APPLICATIONS

MHU-6 could provide scientific evidence that bone-loss conditions such as osteoporosis and osteopenia are not only results of aging but also causes of it. As practical anti-aging medicine, this evidence could lead to better therapeutic interventions to prevent loss of bone and muscle and keep people healthy for longer on Earth.

OPERATIONAL REQUIREMENTS AND PROTOCOLS

After the transfer vehicle arrives at the International Space Station (ISS), the crew transfers the Transportation Cage Unit (TCU) loaded with mice to Kibo module. Six mice for MHU-6 are kept for habitation under microgravity. Samples are returned to Earth aboard a SpaceX Dragon Cargo Vehicle.