After spending the last years of my life pondering on aging and working with people at the end of their lives, I welcomed the challenge of turning one fertilized egg into an adult. This marathon is not over yet.
For reasons unknown to me, it is unusual to be interested in longevity while being female. No matter your gender, it is even more unusual to be interested in life extension and have children. Maybe the self-preservation instinct is strongest in childless/childfree people. But there are a couple of insights I gained about aging since I experienced pregnancy and motherhood and I thought such a different view may turn out useful to some reader out there. I doubt I would have noticed such things if I didn’t have this life experience.
I am not in my 20s anymore and neither is my husband; yet just like with all babies in the world, our daughter was born young. It’s like the clock got reset by shuffling our nuclear DNAs and my mitochondrial one. New theories trying to explain aging appear on the horizon from time to time but none explain this resetting of the clock in sexually reproducing organisms. The latest such theory views aging as being caused by infections. I previously wrote about it here. Indeed, there is an increased bacterial load with aging. Babies are still born young though. Infections in the womb during pregnancy- especially viral ones – lead to severely malformed babies. Some of these babies may be miscarried but none of them is born old. And even when there is no such infection, the womb is not a sterile place.
Coming back to aging and the abundance of diagnoses a typical elderly patient has, I thought geriatrics is a unique medical specialty in dealing with a life stage that produces so much suffering and finally death. I thought that all other physicians had it easy because they dealt with pathological processes which were socially recognized as diseases. But my view was limited by omission.
All that was about to change during the first trimester while I was sitting in the waiting room ready to have some blood work for routine tests. I was tired and nauseous when I glanced my eyes over the referral from my general practitioner which stated a Z code for pregnancy as diagnosis. I remember from my obstetrics rotation during medical school that we shouldn’t refer to pregnant women as patients. Pregnancy is not a disease and such women are subjects. But although pregnancy is not a disease, it causes suffering and it can cause death. It just dawned on me that here I was waiting to get blood drawn while the state health insurance would deduct the costs for what is basically a non-disease. Granted, most evidence-based tests and services are not covered in Romania because of a lack of physicians and a lack/misuse of funds, but in theory everything is covered.
As regards geriatrics, there was already an ICD-10 code for senility – which I never saw in use during my medical residency in geriatrics – that was replaced by another one as “old age” in ICD-11 and lately another time-related code was added giving physicians the option to specify that a disease is aging-related. After working on the proposal to WHO to reconsider aging as a disease because it leads to suffering, it leads to death and there is a dearth of clinical trials, I realized that obstetricians already solved this same problem. Their needed services – both medical and surgical – as well as any lab tests, medication or imagery tests are generally covered by health insurance all over the world. Pregnancy is not a disease and yet this doesn’t mean obstetrics is a medical specialty void of research.
Where obstetricians and paediatricians have it easy is that pregnancy and childhood are physiological processes which do not always cause death. Aging does. If left untreated, aging kills all its victims unless an accident kills them first. Dismissing suffering just because it takes place in an old person is the ultimate form of ageism. Pain is pain no matter who suffers from it. Any biological process has some failure rate: fertility, pregnancy, birth, breastfeeding, childhood. These failure rates are higher or lower depending on access to medical care. But in the case of aging that failure rate is 100%. There are pregnancy-related and childhood-related complications. There are diseases which are more likely to appear in pregnant women and in children. But there is some kind of reward at the end of these stages: a baby at the end of pregnancy, independence at the end of childhood. Aging can be accompanied by wisdom, but what’s the use of it when people dismiss you because you are frail?
Another insight that I got during this pregnancy was already discussed at length in a previous blog post. I mistakenly thought that cellular senescence only happens in the elderly, but I was wrong. Cells become old in the fetus too and unlike the elderly, the fetal immune system is able to destroy such cells once they have done their job. Perhaps this could be a better target for discovering senolytics than the current approach where low-level chemotherapy is tested. Fortunately, the same immune system is now used in clinical trials to solve cancer so maybe this category of drugs – while life-saving for many today – could be improved upon in the next decades by cancer and cellular senescence immunotherapy.
Going to medical school has made me somewhat immune to the dangers of alternative medicine and to the many pieces of obsolete and harmful advice I received during pregnancy and afterwards. Apart from this, the other most useful thing I’ve learned before I got pregnant was swimming. It was the only way I could partially escape gravity during the third trimester. During the 10th month of my overdue pregnancy, I was in the swimming pool barely moving forward when I was thinking to myself how difficult it is to breathe for two people, to pump blood for two people and to carry two people in the same body. I was fortunate that we were only two people and I didn’t have a multiple pregnancy, a risk that increases with age. This is when it occurred to me that pregnancy is similar to parabiosis. There is the placental barrier between the mother and the fetus, but many substances and microorganisms can still pass between the two. Fetal cells can pass through it too and most probably I still have some of my daughter’s cells inside my body now. Fetal microchimerism was demonstrated in many studies during pregnancy and decades afterwards.
If pregnancy is a partial form of parabiosis, you may expect better regeneration in the mother. I don’t feel any younger after this long pregnancy, but I was curious whether there were studies inquiring this. I have found only two such studies on mice where pregnant females regenerated their liver and muscles much better than the non-pregnant ones, but such regeneration entailed hypertrophy instead of hyperplasia as in the young mice, whether the latter were pregnant or not. Unlike hyperplasia, hypertrophy can compensate loss of tissue very fast.
As many of you may know, there are experiments done on heterochronic parabiosis achieved by surgical means between mice of different ages and this sharing of blood circulation led to rejuvenation in the older mouse and aging in the younger one. There is even a clinical trial on older humans who periodically receive transfusions from younger people in an attempt to see whether there is any difference in aging biomarkers. I suspect that there must be some growth signal differential that could explain the initial experiments in parabiotic rodents. What few people know is that such a difference in growth conditions can exist in two closely related humans without any surgical procedure. And I’m not referring to pregnancy where the placenta acts as a barrier and which could at most be viewed as a partial form of parabiosis.
Whenever two or more fetuses share one placenta, their blood circulation can become connected. Such a syndrome is known as twin-to-twin transfusion syndrome. The problem is that in the case of parabiotic twins, one twin develops at the expense of the other and there is a growth gap between the two. In extreme cases, the undeveloped twin may die in the womb. There may be a continuum between a parasitic twin, fetus in feto, conjoined twins and a vanishing twin which died in utero.
As you can see, there are already two models of parabiosis in humans. Pregnancy is a partial type of parabiosis because of the placental barrier. The twin-to-twin transfusion syndrome can be viewed as a complete type of parabiosis, although variants may exist here depending on how many blood vessels got connected between the two. While sharing a common blood network, growth and differentiation signals may be exchanged. Growth relies on an abundance of calories and a cascade of hormones, but administering these in the elderly will not rejuvenate them. Differentiation hormones may be necessary too and this is where I see the importance of studies of parabiosis, especially in the human models of parabiosis as shown above.
Pregnancy was a visceral experience which has left me with scars I didn’t have beforehand, but I don’t regret seeing the world from this perspective. I have lived the surreal experience of having two brains in one body, each wanting to do its own thing. I have this habit of crossing my legs while sitting at my desk, but while pregnant the fetus couldn’t stand it and she kept on kicking until I stayed normally. I also got her frequent kicks if I was working at my desk and I forgot to eat. Eating an apple was not enough to focus again on what I was doing. Those kicks would only stop once I’d eat a proper meal. Whether having a child will increase or decrease my life expectancy, I don’t regret this part of my life. Pregnancy taught me patience I didn’t know I had and motherhood taught me that I can survive with less sleep than I thought it’s humanly possible.
References
Cao, B., Stout, M. J., Lee, I., & Mysorekar, I. U. (2014). Placental microbiome and its role in preterm birth. Neoreviews, 15(12), e537-e545.
O’Donoghue, K., Chan, J., de la Fuente, J., Kennea, N., Sandison, A., Anderson, J. R., … & Fisk, N. M. (2004). Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy. The lancet, 364(9429), 179-182.
Evans, P. C., Lambert, N., Maloney, S., Furst, D. E., Moore, J. M., & Nelson, J. L. (1999). Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. Blood, 93(6), 2033-2037.
Klintschar, M., Schwaiger, P., Mannweiler, S., Regauer, S., & Kleiber, M. (2001). Evidence of fetal microchimerism in Hashimoto’s thyroiditis. The Journal of Clinical Endocrinology & Metabolism, 86(6), 2494-2498.
Michaeli, T. F., Bergman, Y., & Gielchinsky, Y. (2015). Rejuvenating effect of pregnancy on the mother. Fertility and sterility, 103(5), 1125-1128.
Gielchinsky, Y., Laufer, N., Weitman, E., Abramovitch, R., Granot, Z., Bergman, Y., & Pikarsky, E. (2010). Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch. Genes & development, 24(6), 543-548.
Falick Michaeli, T., Laufer, N., Sagiv, J. Y., Dreazen, A., Granot, Z., Pikarsky, E., … & Gielchinsky, Y. (2015). The rejuvenating effect of pregnancy on muscle regeneration. Aging cell, 14(4), 698-700.
Conboy, M. J., Conboy, I. M., & Rando, T. A. (2013). Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging cell, 12(3), 525-530.
Djaafri, F., Stirnemann, J., Mediouni, I., Colmant, C., & Ville, Y. (2017, November). Twin–twin transfusion syndrome–What we have learned from clinical trials. In Seminars in Fetal and Neonatal Medicine. WB Saunders.
Anca Ioviţă is the author of Eat Less Live Longer: Your Practical Guide to Calorie Restriction with Optimal Nutrition ,The Aging Gap Between Species and What Is Your Legacy? 101Ways on Getting Started to Create and Build One available on Amazon and several other places. If you enjoyed this article, don’t forget to sign up to receive updates on longevity news and novel book projects!
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