Imagine aging as a disease that is curable and preventable. This concept challenges our current view that aging is an inevitable process of accumulating age-related diseases and eventual death. Transforming our perspective will require a deeper understanding of the aging process and an arsenal of unique aging models and toolsets in which to test novel hypotheses. Spaceflight offers aging researchers a distinct research model in which to test new ideas that may uncover meaningful discoveries. 

On Earth, aging takes time. Efforts to generate and study normal aging models incur many challenges and costs. In higher-order model organisms used in research, like rodents, aging features could take over a year to develop. Accelerated genetic models of aging, such as Hutchinson-Gilford progeria, Senescence-Accelerated Mouse (SAM), and Werner syndrome shorten the timeline for the appearance of phenotypes. However, these various models do not wholly represent normal aging, displaying only a subset of features. Importantly, some models exhibit confounding characteristics unrelated to aging. Experimental interventions, such as for osteoporosis modeling, can mimic aging in various tissues by surgical immobilization or ovariectomy. However, manipulations face caveats that need to be considered in the interpretation of results. Surgical immobilization, for example, causes disruption of neural inputs to muscle and other tissues, while ovariectomies cause generalized steroid deficiencies.

Spaceflight leads to multi-systemic, adaptive changes in the body, many of which are common features of aging on Earth. Importantly, these changes occur much more quickly in space, without genetic manipulation, thus promoting spaceflight as a unique tool for accelerated aging. Astronauts returning from space missions experience a range of physiological symptoms similar to those seen in the elderly including decreased bone density, loss of skeletal muscle mass and strength, reduced cardiovascular capacity, skin atrophy, and immune dysfunction. At the cellular level, various cell types display markers of genomic instability, telomere attrition, epigenetic alterations, dysregulated nutrient sensing, and stem-cell exhaustion, features consistent with aging. The recent NASA twin-study demonstrates the breadth of tests as well as cellular and physiological parameters that are accessible for the study of age-related changes on the human body. 

Rodents display similar age-related changes in space and have been crucial in understanding accelerated aging through investigative interrogation on a genetic, cellular and organismal level. Measures of bone and muscle atrophy in rodent models are detectable within a few days following arrival at the space station, reflective of the accelerated aging timescale induced by the space environment. Some of these adaptive changes are reversed upon return to Earth, which presents an opportunity to study how the body lessens or even reverses the effects of aging. In order to leverage the use of rodents in future investigations, a recent study housed young and older mice in rodent habitats on the space station to comprehensively evaluate the aging response in microgravity on many tissues and physiological measures. These studies will produce genomic, transcriptomic, and proteomic data from various tissues. Results will push the boundaries of our understanding of the aging process in space and on Earth and serve as the foundation for future studies to test novel hypothesis-driven ideas and promising interventions and drugs. 

The accelerated aging model induced by spaceflight diversifies the available toolset to investigate the aging process and provides a path for expediting the development of effective interventions to improve health as humans age. At Axiom Space, we are developing the next-generation of toolsets that will allow for interrogation of in vitro and in vivo models to address aging-related research questions and accelerate drug discovery efforts.