Life on earth evolved in an environment of gravity; ubiquitous, always there. Take it away, and cellular biochemistry can run awry. Microgravity exposure in higher animals, studied in astronauts who have spent prolonged periods of time in orbit, is a harmful exercise. The longer the exposure, the worse the harms. Many of the changes that microgravity exposure causes to cell and tissue function can be viewed as analogous to those produced by aging. That said, it is important to recognize that microgravity exposure is not aging, just as progeroid conditions resulting from DNA repair deficiency are not aging, the unpleasant dysfunction of type 2 diabetes is not aging, and obesity is not aging. These line items involve the accumulation of forms of damage and dysfunction, but each is a different mix, and the details matter when it comes to trying to draw conclusions about process A when studying process B.
Still, researchers work in an environment that is very sensitive to expenditure of funds and time. Models of degeneration that are at least somewhat similar to aging, and that can be established rapidly, are favored over the old fashioned approach of waiting for animals and people to get old, even though the relevance of the results might be questionable. While one might not think of putting materials into orbit to experience microgravity as a cost-effective approach, it can be when someone else is paying for the necessary facilities in orbit and lift capacity to get there.
An interesting point is made by the authors of today's open access paper about the principle way in which microgravity exposure differs from other models that might resemble aging enough to be interesting, which is that is that people recover from microgravity exposure, and that exposure can be turned on and off quickly. This is an easier alternation of circumstances for scientists to engineer in human subjects than, say, removal of type 2 diabetes or obesity. One could argue that there may well be interesting biochemistry to be found somewhere in this reversal of dysfunction. Will it be in any way applicable to the production of therapies to treat aging? Without looking, that is impossible to say.
Microgravity Therapy as Treatment for Decelerated Aging and Successful Longevity
Given the growing aging population, understanding the mechanisms driving the decline in bodily functions with age has become increasingly essential. Identifying strategies to slow down or even prevent these changes could enhance public health and extend longevity, while yielding significant economic benefits for society. This task is complicated by the long follow-up timeframes needed for such studies, even short-lived rodent models take about three years to observe lifespan changes, and studies in primates can last anywhere from 15 to 30 years. The need for a short-duration human aging model is challenging, and decades of research have not generated one. Recently, we proposed a model that may overcome these challenges.
Gravity plays a crucial role in shaping human physiology, and prolonged exposure to microgravity during space missions can lead to various pathologies that mirror age-related changes. Astronauts frequently experience significant bone density loss, muscle atrophy, cardiovascular deconditioning, immunological, cerebrovascular, cognitive alterations, and metabolic problems. These changes, observed in both aging populations and astronauts in microgravity, reveal striking similarities that highlight the potential of utilizing space as a model for accelerated aging research. In microgravity, aging-like processes are accelerated by up to ten times, occurring over days or weeks rather than years. This makes the space environment a unique model for studying aging in an accelerated format, offering insights that are otherwise unattainable on Earth.
Transcriptomic analyses of human cell lines exposed to both real and simulated microgravity have identified a panel of eleven candidate genes exhibiting consistent differential expression. Upregulated genes include CSGALNACT2, CSNK2A2, HIPK1, MBNL2, PHF21A, and RAP1A, which are involved in pathways such as glycosaminoglycan biosynthesis, chromatin remodeling, RNA splicing, and cytoskeletal organization. In contrast, down-regulated genes such as DNPH1, EXOSC5, L3MBTL2, LGALS3BP, and SPRYD4 reflect impairments in nucleotide metabolism, RNA degradation, chromatin compaction, and intercellular communication, processes that are frequently disrupted during aging. Similar transcriptional signatures have also been observed in human iPSC-derived cardiac progenitor cells cultured aboard the International Space Station, including upregulation of cell cycle regulators (CCND1, CCND2), the proliferation-associated growth factor (IGF2), and the cardiac differentiation marker (TBX3), accompanied by downregulation of extracellular matrix genes. These changes suggest a shift toward increased proliferation and structural remodeling.
Engineered human heart tissues exposed to long-term microgravity similarly displayed downregulation of contractile and calcium signaling genes, alongside increased expression of genes related to oxidative stress, mitochondrial dysfunction, and inflammation, consistent with aging-associated cardiac decline. Additional evidence from single-cell RNA sequencing of immune cells revealed altered expression of genes involved in cytoskeletal organization, IL-6 signaling, and sirtuin-regulated metabolic control, suggesting disruption of immune homeostasis and activation of inflammaging-related pathways. Collectively, these findings define a core set of microgravity-regulated genes in human cells whose altered expression mirrors aging-related molecular deterioration. Their functional roles in key cellular pathways highlight their potential as biomarkers of microgravity adaptation and as therapeutic targets for promoting resilience in aging tissues
View the full article at FightAging
