The research demonstrated that the reproductive system influences general well being and growing older.
The research recognized the unfavorable penalties of disrupting meiosis.
A brand new research in an animal mannequin of growing older signifies a possible motive for why girls who’ve early menopause or different genetic situations affecting the reproductive system are extra susceptible to develop heart problems, diabetes, and dementia.
The new research, led by researchers from the University of Pittsburgh and UPMC and printed within the journal Aging Cell, discovered that disrupting a course of known as meiosis in C. elegans reproductive cells prompted a decline within the worms’ well being and triggered an accelerated growing older gene signature much like that of growing older people.
“This study is exciting because it’s the first direct evidence that manipulating the health of reproductive cells leads to premature aging and a decline in healthspan,” mentioned senior creator Arjumand Ghazi, Ph.D., affiliate professor of pediatrics, developmental biology, and cell biology and physiology at Pitt and UPMC Children’s Hospital of Pittsburgh. “The implications of this finding are profound: It suggests that the status of the reproductive system is important not simply to produce children, but also for overall health.”
A younger C. elegans grownup glowing inexperienced the place a protein has been linked to a fluorescent tag and crammed with soon-to-be-laid eggs that seem as darkish spheres within the mom’s physique. Disruption of meiosis, a course of on which the creation of those eggs relies upon, shortens the animal’s total lifespan and accelerates its growing older. Credit: Scott Keith & Arjumand Ghazi
While the results of growing older on fertility are well-known, analysis prior to now twenty years has began to point out that reproductive health additionally has an influence on human growing older and well being. The difficulty is that it’s troublesome to instantly look at this sort of trigger and impact in people. Ghazi and her colleagues then turned to the Caenorhabditis elegans, a microscopic nematode worm that is a perfect system for growing older analysis as a result of its brief lifetime (three weeks from beginning to dying) and shared genetic pathways with people.
Arjumand Ghazi, Ph.D., affiliate professor of pediatrics, developmental biology, and cell biology and physiology on the University of Pittsburgh and UPMC Children’s Hospital of Pittsburgh. Credit: UPMC
The researchers studied meiosis, a form of cell division current in all animals from yeast to people that occurs completely in cells destined to provide sperm or eggs. They found that animals with mutations in meiosis genes had shorter lives than their non-mutated counterparts. The mutants additionally had worse general well being rankings, together with untimely reductions in mobility, muscular perform, and reminiscence.
“The exciting part of this healthspan work was that these animals also showed signs of disrupted protein homeostasis,” mentioned Ghazi. “Disruption to the steadiness of proteins inside cells is on the coronary heart of age-related neurodegenerative ailments, like Alzheimer’s disease.”
When the researchers improved protein homeostasis in the worms, some loss of lifespan was prevented. These findings point to disrupted proteostasis as a key mechanism linking reproductive health and aging.
Next, the team looked at gene expression changes in C. elegans. At day 1 of adulthood, meiosis mutants expressed genes that were remarkably similar to those normal worms wouldn’t express until day 10.
“In human terms, it’s like someone in their early 20s having the physical appearance, physiology, and gene signatures of a 70-year-old,” explained Ghazi. “Messing with meiosis has dramatic effects on healthspan and accelerates aging in C. elegans.”
Many of the same genes control aging in worms and humans. So the researchers asked if the meiosis mutants’ gene signature had any similarities with the genes of aging humans. They found that this was, indeed, the case — a notable finding as it suggests that disrupting the reproductive system may produce similar changes from worms to humans.
Since C. elegans can be used to make fundamental discoveries not possible in humans and more complex systems, this discovery opens up great possibilities for understanding how the reproductive system shapes aging, said Ghazi.
She is now planning to partner with UPMC Magee-Womens Hospital and Magee-Womens Research Institute to further probe this question in human patients who, due to genetic disease, undergo extremely premature menopause and exhibit complications such as heart disease, autoimmune disorders, and osteoporosis.
“Informed by our work in C. elegans, we want to develop a panel of age-related genes and use this to screen patients’ blood and saliva,” said Ghazi. “If we see evidence of the same genes being elevated in patients, it would be a major first step toward extending such studies to women who undergo early menopause and early infertility.”
Ghazi hopes that eventually this work could inform tests for early detection of health impairments triggered by reproductive abnormalities and new treatments or repurposing of existing drugs to treat such age-related diseases.
Reference: “Meiotic dysfunction accelerates somatic aging in Caenorhabditis elegans” by Julia A. Loose, Francis R. G. Amrit, Thayjas Patil, Judith L. Yanowitz and Arjumand Ghazi, 29 September 2022, Aging Cell.
DOI: 10.1111/acel.13716
The study was funded by the National Institutes of Health.
