The study identified the negative consequences of disrupting meiosis.
A new study in an animal model of aging indicates a potential reason for why women who have early menopause or other genetic conditions affecting the reproductive system are more prone to develop cardiovascular disease, diabetes, and dementia.
The new study, led by researchers from the University of Pittsburgh and UPMC and published in the journal Aging Cell, found that disrupting a process called meiosis in C. elegans reproductive cells caused a decline in the worms’ health and triggered an accelerated aging gene signature similar to that of aging humans.
“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,” said senior author Arjumand Ghazi, Ph.D., associate 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.”
While the consequences of aging on fertility are well known, research in the past two decades has started to show that reproductive fitness also has an impact on human aging and health. The issue is that it is difficult to directly examine this kind of cause and effect in humans. Ghazi and her colleagues then turned to the Caenorhabditis elegans, a microscopic nematode worm that is an ideal system for aging research due to its short lifetime (three weeks from birth to death) and shared genetic pathways with humans.
The researchers studied meiosis, a kind of cell division present in all animals from yeast to humans that happens exclusively in cells destined to produce sperm or eggs. They discovered that animals with mutations in meiosis genes had shorter lives than their non-mutated counterparts. The mutants also had worse overall health ratings, including premature reductions in mobility, muscular function, and memory.
“The exciting part of this healthspan work was that these animals also showed signs of disrupted protein homeostasis,” said Ghazi. “Disruption to the balance of proteins inside cells is at the heart of age-related neurodegenerative diseases, 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.
The study was funded by the National Institutes of Health.
If “…disrupting meiosis…” results in “…heart disease, autoimmune disorders, and osteoporosis.” in prematurely menopausal women it suggests to this lay investigator it involves food allergies, a loss of estrogen production followed with a high serum level of uric acid and, probably, a medically undiagnosed calcium deficiency. It’s amazing how the continuing failure to learn about my kind of food allergies (e.g., THE PULSE TEST, Arthur F. Coca, MD, 1956); fundamental to all things health and wellness in humans) in conjunction with FDA approved food poisoning (e.g., added MSG, minimally, since 1980) in medical schools can keep leading to new discoveries of old facts. For me it now poses this question: is it inherited allergies, an inherited genetic mutation and/or one and the same?
Could prescribed contraceptives, oral or implants be associated with early menopause? What effect do these contraceptives have on the ovaries? Appears to be increasing polycystic ovaries and endometriosis in many women I am involved with for breastfeeding complications.
How many times have women been told that they don’t need their ovaries anymore if the are getting a hysterectomy. Doctors have routinely done this. Perfectly fine ovaries. I have had more than one friend who has asked her surgeon to preserve her ovaries and the doctors sneered at them.
If our ovaries were on the outside like testicles…
I had a total hysterectomy nearly 5 years ago, in my early 40’s. Never have I felt better, I have none of the problems listed above and feel better than I ever have. I look younger than I am, have more energy and am enjoying a more full life without being dragged down by my reproductive system. I am not affected by diabetes, osteoporosis or heart problems. My libido is through the roof. I guess there are exceptions. What’s wrong with aging again?! What needs to be studied is how to rid America of its aging bias.
As an amateur scientist, are you on hormone therapy?
I always assumed our bodies evolved to last as long as we were effectively reproducing so this seems reasonable.
I think this study relates to biological females only.
I willl be 81 in December. I went threw a needless radical hysterectomy ( I found out later) in the 70’s. Was then put on Estrogen pills, then patches and did not get off this med until my late 50’s as my dr. stated it may cause brest cancer.Am told I look about 60ieh. My family has history of diabetes on my fathers side. I developed diabetes at 68 yrs. old . I recently in the past 2 years have heart problems due to hypertension with 3 stents. Most heart drugs make me develop all the SIDE EFFECTS from these drugs ergo my blood pressure is usually elevated. However not bad for almost 81 years old huh!
Well, the true problem is that women sunbath all day without sunscreen smoking the whole time.
I don’t sunbathe or smoke so no, you’re wrong!!!! But I get you, there’s so many factors to aging not just environment and exposures it just goes on and on…..
To be denied fertility treatment through health insurance has been devastating and cruel. I knew that infertility was a sign of something much bigger that is wrong with my body and needs to be fixed. Now I have no children, suffer from many of the conditions mentioned in this article, and feel much older than I should.
THIS RESEARCH IS SO IMPORTANT!!! THANK YOU AND GOOD LUCK!!!
A Dr here said that her patients had a development of endometriosis and PCOS. Because they used birth control. I had both by the time I was 14 years old and never used birth control until I was 20 years old. People need to think that the role that genes play is fundamental in the development of health conditions. Especially in the reproductive health of a woman.
The role that the consumption of foods, types of foods and, the environment play are secondary to the genetical factors. The way that food is processed in The US is so harmful. Compared to the way they are processed in Europe. For me it plays a significant role. This research is so interesting. I wish I could find a way to follow it more in depth.
I would like to ask the lead researcher if this can take into account the trans females and trans males that go into estrogen and testosterone therapy for their transition. I ask this because if the people that are detransitioning and talking about the harmful effects that the hormone replacement. Did to their body and it’s not talked about more. How maybe going against that can lead into a more significant aging process and damages to their health. Just like the patients that get a y-roux like me. Now I am only discovering how much damage in a cellular level the malnutrition variable has played in my health. I have a lot of questions to the lead researcher.
paige, me too.never felt better after my hyster.has not badly affected anything minus scars and unnecessary appendix removal pain.think med ind is using this to sell more hormone replacement which causes disasters
Am interested to see the progress of this research. I am 50 and had a complete hysterectomy 8 years ago because of being BRCA 2+. After the surgery, the severe depression I had previously vanished however over that 8 years I’ve developed Sjogren’s and osteopenia. I get lots of calcium and vitamin D. I really think vitamin D levels are overlooked way to often. I insisted to my doctor to have my vitamin D levels tested and they were found to be low.
I feel like there should be a whole protocol with vitamin panels for post hysterectomy/menopause care to help to delay some of these internal aging issues. I was unable to take hormonal therapy as I have a very strong history of breast cancer on my mothers side. On the upside, I have not yet developed breast cancer at an early age as both mom and grandmother had.
I’m 57 years old and had a complete hysterectomy, due to endometriosis, when I was 36. I wore a hormone patch up until this past summer. My health is good, but my skin is a little lax.
Complete hysterectomy at 28. Had polycystic ovaries and had a miracle child at 23. I am 60 and have chronic illnesses since 35. I didn’t tolerate hormone replacement therapy so didn’t take any. This research makes my life make sense. Insulin dependant, high blood pressure, heart disease, kidney failure and and degenerative nerve disease oh, and pain all over.
Perhaps my comments from the 11th can provide you with some additional understanding of your problems and possible solutions. Your problems started shortly after the FDA approval of the expanded use of added MSG as an alleged ‘flavor enhancer’ in 1980. Lots of information online about dealing with MSG but not so much about my kind of food and food additive allergies. Good luck.
Curious about something…they used worms in this study. If one of the side effects is memory loss, how did they test for that? I don’t think we need a study to tell us that the longer we keep our female parts the better it is for our health. As long as our parts are healthy.