Mother’s Curse

It’s a harsh world for us men. Oh, sure, we’ve got all the political and economic power, and we’ve got most of the guns, but step into a senior citizens’ center and you’ll notice the preponderance of elderly women. Men die younger, on average. I’m also acutely aware of the growing disparity as we get older: my wife seems to be aging at about half the rate I do. If you’ve been watching House of Cards on Netflix, you may have noticed that the character played by Kevin Spacey, face a bit puffy and deeply lined, is married to a character played by Robin Wright (Princess Buttercup!) who is looking fabulous: mature, a bit severe, but still looking great. This situation is not unusual.

This is not fair. The average life expectancy of women in the US is 80 years, while men live to be about 75.

Why?

It’s not sufficient to say it just is that way; we have to dig deeper and figure out the differences. Part of the answer is that human males have a youthful history of riskier behavior than females, but again we have to ask why: what is driving men to do stupid stunts that lead to higher rates of mortality? But even if we have a good answer for that one, it doesn’t address that other problem, the accelerated rates of male senescence. I’ve survived my heightened risk of death by misadventure, so why am I getting increasingly decrepit while women my age are looking more fit and healthy?

Part of the answer may be in your genes, your mitochondria, and evolution. Mitochondria play an extremely important set of roles in aging. They hold the keys to cell death and responses to cancer; most apoptotic responses are triggered by the release of signals from the mitochondria. Mitochondria are the agents that produce energy for the cell, and also produce reactive oxygen species in their normal operation. You may be hearing the hype about anti-oxidants, and are diligently taking cofactors and vitamin pills to reduce, hypothetically, the deleterious effects of these avidly destructive molecules, but the primary source of those oxidants is by the activity of mitochondria. There are overt hereditary diseases of mitochondria, like LHON and MELAS which reveal the importance of mitochondria in normal metabolism, but there are also other diseases like Alzheimer’s and Parkinson’s that have a mitochondrial component that plays a role in the severity of the effects. And aging is a disease that is also associated with mitochondrial function.

But wait, you’re thinking, mitochondria are equally important in men and women, so how can they account for a difference between the sexes?

Keep in mind that mitochondria are not magically autonomous. They contain about 35 genes essential for metabolism, and use about a thousand more that come from the nuclear genome, so there’s a significant amount of information shuttling back and forth between the nucleus and the mitochondrion. There are also epigenetic influences: mitochondrial states are known to modulate states of DNA methylation in the nucleus. And obviously, there are subtle differences in between the nuclear genomes of men and women, and probably even greater epigenetic differences between the two. So here we have two complex genetic units, the nucleus and the mitochondria, interacting with one another, and in a perfect world they’d be beautifully fine-tuned and singing in harmony with one another…but at the same time we have sex differences in the nuclear genetics, which complicates the problem of matching the two.

And this is where evolution steps in. There’s a genetic problem here.

The inheritance of mitochondria is asymmetric: you only get them from your mother, and your father makes no mitochondrial contribution at all. Your father’s mitochondrial contribution dies with him and is not passed on. What does that mean? It means that there can be no selection to fine tune mitochondria to the male nuclear genome. As a recent paper by Wolff and Gemmell explains:

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