Are Skeletal Muscle Changes during Prolonged Space Flights Similar to Those Experienced by Frail and Sarcopenic Older Adults?

Abstract

Microgravity exposure causes several physiological and psychosocial alterations that challenge astronauts’ health during space flight. Notably, many of these changes are mostly related to physical inactivity influencing different functional systems and organ biology, in particular the musculoskeletal system, dramatically resulting in aging-like phenotypes, such as those occurring in older persons on Earth. In this sense, sarcopenia, a syndrome characterized by the loss in muscle mass and strength due to skeletal muscle unloading, is undoubtedly one of the most critical aging-like adverse effects of microgravity and a prevalent problem in the geriatric population, still awaiting effective countermeasures. Therefore, there is an urgent demand to identify clinically relevant biological markers and to underline molecular mechanisms behind these effects that are still poorly understood. From this perspective, a lesson from Geroscience may help tailor interventions to counteract the adverse effects of microgravity. For instance, decades of studies in the field have demonstrated that in the older people, the clinical picture of sarcopenia remarkably overlaps (from a clinical and biological point of view) with that of frailty, primarily when referred to the physical function domain. Based on this premise, here we provide a deeper understanding of the biological mechanisms of sarcopenia and frailty, which in aging are often considered together, and how these converge with those observed in astronauts after space flight.

Healthy aging: when periodontal health matters

“…Finally, Kawamura and colleagues 112 demonstrated that chronic exposure of mice to the LPS of Porphyromonas gingivalis (P. gingivalis), one of the major pathogenic factors for periodontitis 113,114 increased muscle atrophy participating in the development of physical frailty and sarcopenia. Overall, the aforementioned mechanisms support the interrelation between the impairment of the functionality of immune cells (immunosenescence), the increased incidence and severity of infections observed in older subjects, and the impact on frailty 103 .…”

“…Frailty is a complex physiological syndrome characterized by increased susceptibility to stressors and reduced physiological reserves that, from a biological point of view, is driven by a gradual and lifelong accumulation of molecular defects, including those affecting the immune system. In this regard, several proofs have corroborated such a theory 103 . For instance, Leng et al 104 provided the first evidence of a direct link between frailty and inflammation, showing that community-dwelling older frail individuals presented with higher serum IL-6 levels than non-frail subjects.…”

Aging and putative frailty biomarkers are altered by spaceflight

“…When this condition is driven by aging, it is defined as primary sarcopenia 9 . Interestingly, muscle loss in astronauts shares similarities with sarcopenia in the elderly, especially during long duration spaceflight, and could be interpreted as a sarcopenia-like syndrome 17 , 18 .…”

Circadian regulation in aging: Implications for spaceflight and life on earth

“…Aging phenotype results from alterations in telomere length, epigenetic regulation, and mitochondrial function, along with dysregulations in nine other processes (proteostasis, macroautophagy, cellular senescence, stem cell exhaustion, intercellular communication, chronic inflammation, dysbiosis, genomic instability, and nutrient‐sensing), which are altogether referred to as the hallmarks of aging (López‐Otín et al, 2023 ). Interestingly, recent studies associate aging to spaceflight with contradictory conclusions (Biolo et al, 2003 ; Cannavo et al, 2022 ; Garrett‐Bakelman et al, 2019 ; Honda et al, 2012 ; Ma et al, 2015 ; Malhan et al, 2023 ; Nwanaji‐Enwerem et al, 2020 ; Otsuka et al, 2019 ; 2022 ; Wang, 1999 ), while some of the studies report an anti‐aging impact of spaceflight, others observed progressive aging due to spaceflight. Whether the anti‐aging impact of spaceflight correlates with the “twin paradox” (Gron, 2006 ) based on the theory of relativity coined by Albert Einstein, which proposes that an individual in Space ages slower compared to his/her biological twin on Earth, remains to be shown.…”