The balance between fertility and longevity

Humans have always been intensely interested in longevity. Over the years, efforts to live a long and healthy life have come in many forms, with most focusing on diet. And rightly so–the food we eat has a tremendous influence on aging long and well.

I’ve posted before about mTOR. mTOR has become the keystone to many people’s views on longevity, and I’ve written about it previously. Briefly, mTOR is a protein within cells that powerfully regulates the growth and maturity of a cell. When mTOR is turned on, the cell wants to grow and mature. When mTOR is turned off, other proteins push the cell to undergo a process called autophagy. This latter process is considered essential to longevity–by blocking mTOR, the cells stay “younger”.

This view that mTOR inhibition is a key to eternal youth isn’t without support, especially in insect and animal studies [1]. Importantly, there is no evidence in humans that mTOR inhibition can extend lifespan. However, there is evidence in humans that inhibiting mTOR causes significant problems when it comes to fertility.

Of course, despite the bad reputation with aging (deserved or not), mTOR is an essential protein in cells, and while its primary role may be to signal growth in cells, it plays an important role in reproduction in males and females.

In females, the initial event in reproduction is the production and release of the ovum–the egg–from the ovaries. Of the many proteins (and hormones!) involved in this process, mTOR is essential. When mTOR is prevented from working, the ovum fails to develop and ovulation is stopped [2].

Similarly, in males, the essential event is the production of sperm. As with the ovum, mTOR is critical in promoting the sperm to fully mature and function. In men taking mTOR inhibiting drugs, sperm production is dramatically reduced [3].

Beyond the direct effect on mTOR inhibition on blocking essential processes in reproduction is the effect on sex hormone production. mTOR is essential in the ovaries producing estrogens and the testes producing testosterone (though each also produces the other) [4,5].

Altogether, these data provide an interesting paradigm–efforts that (may!) promote longevity also reduce fertility. This has obvious ramifications if you’re interested in fertility, but because sex hormone production is also affected with mTOR inhibition, the consequences may also be relevant for people past child-bearing years. After all, a reduction in sex hormones with aging is a key concern (and why so many men and women are interested in sex-hormone replacement therapy).

All of this very technical conversation does have a practical application–mTOR could matter for longevity, but it definitely matters for fertility and sex hormone production. A diet can be tailored to possibly enjoy the best of both. This would be activating mTOR for brief periods, giving it time to play its essential role, but ensuring other periods of time when mTOR is turned down.

Most of the attention on mTOR activation has focused on amino acids (that come from dietary protein) [6]. Interestingly, amino acids only turn on mTOR temporarily–it’s up, then down. However, insulin turns on mTOR much more (and for longer) than amino acids do [7]. This is a result of how amino acids and insulin behave. While amino acids usually clear the blood (and stop activating mTOR) within about 45 minutes, insulin can remain elevated for hours. And by the time insulin starts to return to fasting levels, it’s often spiked back up due to frequent eating.

Focus on restricting processed starches and sugars, while being liberal with protein and fat. With this, mTOR will be turned on when you want it, and off the rest of the time.

References

1. https://www.karger.com/Article/Fulltext/484629
2. https://www.frontiersin.org/articles/10.3389/fendo.2019.00692/full
3. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-6143.2007.01929.x
4. https://www.frontiersin.org/articles/10.3389/fendo.2019.00692/full
5. https://academic.oup.com/biolreprod/article/83/Suppl_1/420/2955862
6. https://www.nature.com/articles/nrm3522
7. https://pubmed.ncbi.nlm.nih.gov/21702994/