The secret to cellular youth may lie in maintaining a small nucleolus—a dense structure within the cell nucleus—according to investigators at Weill Cornell Medicine. These findings were uncovered in yeast, a model organism renowned for its role in making bread and beer, yet surprisingly similar to humans at the cellular level.

The study, published Nov. 25 in Nature Aging, may lead to new longevity treatments that could extend human lifespan. It also establishes a mortality timer that reveals how long a cell has left before it dies.

As people get older, they are more likely to develop health conditions, such as cancer, cardiovascular disease and neurodegenerative diseases.

Surprisingly, the organoids were still healthy when they returned from orbit a month later, but the cells had matured faster compared to identical organoids grown on Earth—they were closer to becoming adult neurons and were beginning to show signs of specialization. The results, which could shed light on potential neurological effects of space travel, were published on October 23, 2024, in Stem Cells Translational Medicine.

“The fact that these cells survived in space was a big surprise,” says co-senior author Jeanne Loring, PhD, professor emeritus in the Department of Molecular Medicine and founding director of the Center for Regenerative Medicine at Scripps Research. “This lays the groundwork for future experiments in space, in which we can include other parts of the brain that are affected by neurodegenerative disease.”

On Earth, the team used stem cells to create organoids consisting of either cortical or dopaminergic neurons, which are the neuronal populations impacted in multiple sclerosis and Parkinson’s disease—diseases that Loring has studied for decades. Some organoids also included microglia, a type of immune cell that is resident within the brain, to examine the impact of microgravity on inflammation.

Abstract. Research conducted on the International Space Station (ISS) in low-Earth orbit (LEO) has shown the effects of microgravity on multiple organs. To investigate the effects of microgravity on the central nervous system, we developed a unique organoid strategy for modeling specific regions of the brain that are affected by neurodegenerative diseases. We generated 3-dimensional human neural organoids from induced pluripotent stem cells (iPSCs) derived from individuals affected by primary progressive multiple sclerosis (PPMS) or Parkinson’s disease (PD) and non-symptomatic controls, by differentiating them toward cortical and dopaminergic fates, respectively, and combined them with isogenic microglia. The organoids were cultured for a month using a novel sealed cryovial culture method on the International Space Station (ISS) and a parallel set that remained on Earth. Live samples were returned to Earth for analysis by RNA expression and histology and were attached to culture dishes to enable neurite outgrowth. Our results show that both cortical and dopaminergic organoids cultured in LEO had lower levels of genes associated with cell proliferation and higher levels of maturation-associated genes, suggesting that the cells matured more quickly in LEO. This study is continuing with several more missions in order to understand the mechanisms underlying accelerated maturation and to investigate other neurological diseases. Our goal is to make use of the opportunity to study neural cells in LEO to better understand and treat neurodegenerative disease on Earth and to help ameliorate potentially adverse neurological effects of space travel.

Researchers at the Icahn School of Medicine at Mount Sinai have been awarded a $21 million grant from the National Institute on Aging (NIA) of the National Institutes of Health (NIH), to further advance understanding of an aging-related hormone known as follicle-stimulating hormone (FSH), including its potential role in obesity, osteoporosis, and Alzheimer’s disease. The work could lead to the development of new treatments for these and other conditions involving aging.

This is a collaborative effort with the NIA, led by Mone Zaidi, MD, PhD, Director of the Center for Translational Medicine and Pharmacology at Icahn Mount Sinai, and Clifford J. Rosen, MD, at the MaineHealth Institute for Research in Scarborough, Maine. Dr. Zaidi and Dr. Rosen are Program Directors, and principal investigators of individual projects are Anne Schafer, MD, at the University of California in San Francisco, as well as scientists at Icahn Mount Sinai, including Tony Yuen, PhD, Associate Professor and Research Director of the Center for Translational Medicine and Pharmacology, and Daria Lizneva, MD, PhD, Associate Professor of Pharmacological Sciences. Together, the investigators will work toward translating their findings into viable treatments for patients.

“We are delighted that the NIH has recognized the potential of our work by awarding this generous grant,” says Dr. Zaidi, the Mount Sinai Professor of Clinical Medicine at Icahn Mount Sinai. “Our focus for more than 25 years has been on identifying actionable targets for major public health diseases. This research offers the potential for a new drug for menopause and could also possibly help advance treatments for Alzheimer’s disease, obesity, and osteoporosis, affecting millions of people worldwide.”