The link between less calories, longer life, and healthier eggs

For years scientists have been obsessed with identifying factors that are associated with increasing longevity. Usually most of the recommendations revolve around things to avoid, like a sedentary lifestyle, smoking, excessive alcohol, fatty foods, and refined sugars. But what interventions can we actively pursue that might help in this respect?

Strangely enough, one factor that has also been linked to longer lifespan is a hypocaloric diet. In other words, longevity seems to be increased by pursuing a diet that is, while well-balanced, containing 30% less calories than one would normally intake. In fact,  a recent study in mice demonstrated that young mice subjected to diets that mimic fasting had extended longevity, lowered visceral fat, reduced cancer incidence, rejuvenated the immune system, and retarded bone mineral density loss. In older mice, such diets promoted development of neurons in the brain and improved cognitive performance. Data has also accumulated in primate models that is also very encouraging.

How can it ever be considered a good thing health-wise to nearly starve, to observe a diet that has you always feeling a bit hungry? It may stem from the simple fact that we were never designed to live in an environment where food is always abundant. Our bodies were perfected over time to deal with difficult conditions that required us to exert a lot of physical activity in order to obtain even a meager supply of food to sustain ourselves. When we exercise less and eat more, our bodies may very well be placed into a state of turmoil physiologically, and unsurprisingly we find ourselves with heretofore unknown levels of obesity, diabetes, hypertension, and even perhaps neurological decline. At the molecular level, we know that animals who consume healthy diets, and even moreso animals that consume hypocaloric diets, show less evidence of inflammation and oxidative stress in the body. It would seem that lower cellular metabolism leads to lower cellular waste products, and this in turn promotes a healthier environment for cells. This beneficial effect of caloric restriction seems to be extended to ovaries and oocytes as well and this has always intrigued me as a Reproductive Endocrinologist.

It has been discovered that sirtuins, which are a specific group of enzymes termed deacetylases, are increased during the starvation process, and since this revelation, data has been accruing that suggest that enhanced sirtuin activity is responsible for many of the beneficial effects associated with hypocaloric diets. In addition to modulating the inflammatory response and metabolism, sirtuins also help to repair DNA. It’s not hard to see how these effects might help prolong cellular well-being and in turn promote a longer life span of the individual as well as of the ovary. Given the fact that the limiting step in reproduction is most often the acquisition of a healthy (meaning chromosomally normal) oocyte, any compound that can diminish the negative effects of aging upon oocyte chromosomal stability could potentially be a boon for fertility.

Several research studies have been quite encouraging. For example, sirtuins have been demonstrated to be associated with enhanced oocyte lifespan and improved integrity of oocyte DNA. 1 2 3

So, do we need to semi-starve ourselves to live and/or reproduce longer? Some people think so, and are actively pursuing this lifestyle. Only time and high quality prospective studies will tell if it ultimately has merit. Until then, I recommend a healthy balanced diet that gets you into the normal range for your BMI. Probably the mere avoidance of overweight status is close enough to allow one to achieve their optimal state of health (both ovarian and otherwise).

If you are experiencing premature ovarian decline, consult with your fertility specialist about the dietary supplement resveratrol, which is a known stimulator of sirtuin. The rationale for its consideration would be that resveratrol may facilitate some of the health effects that a hypocaloric diet can foster without actually forcing one to adopt this dietary pattern. Studies in animals would seem to bear this out, and resveratrol has been linked to delayed menopause, decreased frequency of chromosomally abnormal oocytes, and even higher fertilization rates. 4 5 6 

Resveratrol supplements abound, but it can also be found naturally in low concentrations in the skin of red grapes (and hence, red wine) and blueberries. Food for thought!

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[1] L. Zhang, L. Han, R. Ma, X. Hou, Y. Yu, S. Sun, Y. Xu, T. Schedl, KH. Moley, Q. Wang  Sirt3 prevents maternal obesity-associated oxidative stress and meiotic defects in mouse oocytes[2] T. Zhang, Y. Zhou, L. Li, HH. Wang, XS. Ma, WP. Qian, W. Shen, H. Schatten, QY. Sun  SIRT1, 2, 3 protect mouse oocytes from postovulatory aging [3] L. Han, J. Ge, L. Zhang, R. Ma, X. Hou, B. Li, K. Moley, Q. Wang  Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte

[4] M. Liu, Y. Yin, X. Ye, M. Zeng, Q. Zhao, DL. Keefe, L. Liu Resveratrol protects against age-associated infertility in mice.

[5] N. Itami, K. Shirasuna, T. Kuwayama, H. Iwata  Resveratrol improves the quality of pig oocytes derived from early antral follicles through sirtuin 1 activation

[6] R. Ma, Y. Zhang, L. Zhang, J. Han, R. Ruj  Sirt1 protects pig oocyte against in vitro aging