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Feb 06 2013

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:

The asymmetry in mtDNA inheritance, however, becomes problematic in the case of traits that affect exclusively males and shared traits that, if compromised, have a disproportionally greater effect on males than females. In this instance mutations that harm males but leave females unaffected will escape purifying selection and lead to the accumulation of a mutational load in the mitochondrial genome detrimental to male-specific traits; a scenario described as mother’s curse. Male reproductive traits have long been in the limelight as ideal candidates to fall victim to this mechanism. Compelling support for such male specific reproductive effects comes from a recent study. Using a fly model, Innocenti et al. expressed five different naturally occurring mtDNA variants alongside a standardized nuclear genome and profiled the resulting gene expression within these mitolines. A pronounced asymmetry in nuclear gene expression profiles was observed between males and females with the majority of affected transcripts being overexpressed only in males and highly over-represented in male reproductive tissues. Overall, this study suggests that naturally occurring mtDNA variability exerts a much stronger effect on male fitness than it does on female fitness, strongly supporting the concept of mother’s curse. This finding is well in line with a range of studies that identified either mtDNA variants or specific mito-nuclear lineages as associated with male reproductive impairment across a variety of taxa.

The name “mother’s curse” is a bit unfair. It’s not just the maternal contribution that affects us males, but the fact that our nuclear genomes (which are derived from both our mother and father) may be subtly out of synch with our mitochondrial genomes (which are derived exclusively from our mother). Don’t blame your mom for your wrinkles and grey hair, guys — you should still call her on Mother’s Day.

Two other points to make: 1) this phenomenon of greater male senescence is universal, and seems to be found all across multicellular phyla. Apparently, earlier death is something that actually is a guy thing. 2) While there aren’t opportunities to directly select for greater compatibility between mitochondria and nuclei in males, don’t count inclusive fitness out. Male mortality can obviously effect female survival, so you can have indirect effects that promote better male survival.

It suggests that males are not only subject to heightened risks of disease and infertility, but implies that across almost all eukaryotic life they will have shorter lives simply as a consequence of the maternal inheritance of the mitochondrial genome. The diminutive mtDNA plays David to the nuclear Goliath because of the inability of selection to eliminate mutations harmful to males, but neutral or beneficial to females, under most scenarios. Recent theoretical work suggests that, under scenarios in which there are high levels of positive-assortative mating and strong inclusive fitness, the indirect costs to females may be great enough to enable selection to remove mtDNA types deleterious to males but not females. However, on the whole there is little opportunity for deleterious mtDNA mutations to be selectively eliminated from populations, unless they have direct fitness costs to females.

Hmmm. I should probably do things that make sure my health and fitness are correlated with my female partner’s health and fitness, so that my mitochondrial-nuclear matching is relevant to the survival of my offspring. Yeah, that’s the ticket. I should start consciously thinking that way.


Wolff JN, Gemmell NJ (2013) Mitochondria, maternal inheritance, and asymmetric fitness: Why males die younger. Bioessay 35(2):93-9. doi: 10.1002/bies.201200141.

35 comments

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  1. 1
    Tabby Lavalamp

    Nature is misandry!

  2. 2
    Beatrice, an amateur cynic looking for a happy thought

    Female privilege!

  3. 3
    L E

    I wonder how this effects species without genetic sex determination? Actually that would be a good test – you would expect that if mito-nuclear conflicts are the cause of male biased senescence that it would be absent in those species.

    I should probably go read the paper, shouldn’t I?

  4. 4
    John Small Berries

    The average life expectancy of women in the US is 80 years, while men live to be about 75. Why?

    Henny Youngman posed a similar question, and then immediately answered it: “Why do Jewish men die before their wives? Because they want to.”

  5. 5
    left0ver1under

    I wouldn’t doubt that the shorter average life span has a lot to do with the natural birth rates. Everything I’ve read says that (without selective abortion or infanticide of girls) the male to female ratio is about 101-102 boys for every 100 girls. To me it looks like the greater number of males makes up for the shorter life span, nature’s way of equalling out the genders over time.

  6. 6
    Tony! The Fucking Queer Shoop!

    So is this the post we should direct all MRAs to when they ask “what about the menz?”
    Hmmm…on second thought, no. They will find a way to turn this post into commentary on how women have it so much better than men and they really are discrminated against.

  7. 7
    Jackie the wacky

    I thought the Mother’s Curse was, “May you have children who behave just like you!”

    *shooting star*
    The more you know.

  8. 8
    eddyline

    So…the implication is that multicellular species are evolving beneficial traits for females, but not necessarily for males—which should continue to widen the longevity gap, right? *Spockbrow* Fascinating.

  9. 9
    cervantes

    “ou 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 . . .”

    If you are doing that, save your money. It doesn’t work. Here’s the latest met-analysis, specifically concerning cardiovascular disease, but taking anti-oxidants has no benefit with respect to cancer, or general aging, or anything else. In fact, there can be harmful effects. Vitamin pills in general, for people with even half-decent diets and no specific diseases for which there is an indication, are completely worthless. They are essentially a scam. Just so y’know.

    As for the inclusive fitness thing, sperm from old men is not worth very much, so I doubt that is ever a meaningful effect.

  10. 10
    Chris Clarke

    sperm from old men is not worth very much

    Aw hell.

    *cancels etsy account”

  11. 11
    twas brillig (stevem)

    I always question the legitimacy of the statistics behind the life expectancy figures. I remember, a few decades a go the claim was that the difference was simply more men smoke than women, thus non-smokers live the same length. I really don’t think that claim holds true anymore. (do more men smoke than women, still?) Secondly, just saying the average age of death for women is higher than men could well include higher mortality of male infants or risky behavior by male teenagers, etc. So, what is the life expectancy of the typical 50 y.o. non-smoker, male vs female? etc. etc, but this can go on and on; narrowing the sample size by more and more conditions to make any kind of conclusion about male vs female longevity.

    Sorry to go on and on, just letting my SPC training take over for a minute.

  12. 12
    Janet Camp

    “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”

    Or maybe Robin Wright has had numerous cosmetic surgery procedures and Spacey has not –or had fewer. Honestly, what an idiotic way to try to demonstrate a point.

  13. 13
    Howard Bannister

    @stevem: that’s a solved problem.

    No, seriously. When they went to design Social Security they knew that infant mortality rates meant that life expectancy for somebody who reached sixty-five was higher than general life expectancy–which was sixty-five. If you made it to sixty-five it was roughly the same as it is now. (actually, better, for some people in particular minorities)

    They could solve that then.

  14. 14
    intelligentdesigner

    My wife just found out that from her 23AndMe test results that her mitochondrial haplotype is D4a which is associated with extreme longevity.

    This blog entry is interesting but I do have one question in regard to this statement:

    there’s a significant amount of information shuttling back and forth between the nucleus and the mitochondrion

    Please define information.

  15. 15
    Rev. BigDumbChimp

    Please define information.

    Here we go.

    Weren’t you banned from the blog or am I confusing you with someone else who goes by intelligentdesigner and is obsessed with and fails miserably and trying to define information in a way he can cram it into some miserable proof of ID?

  16. 16
    Rev. BigDumbChimp

    first line was of course supposed to be blockquoted

  17. 17
    Thorne

    I thought the Mother’s Curse was, “May you have children who behave just like you!”

    My mother used to say, when I was a particularly bad boy, “May you have two just like you!”

    And damn it, that’s just what happened! The curse works!

  18. 18
    Nick Gotts

    Hmm, I’ve come across at least two other hypotheses:
    1) It’s down to size. Smaller people live longer, and women are on average smaller than men. It would be interesting to look at species where females are larger – are they still longer-lived? Among mammals this is not common, but hyenas, at least some whales, and naked mole-rats are examples. Among raptors, females are larger, not sure about other birds.
    2) Male reproductive success in the period of peak health is likely to have greater variance than female; so it will pay selectively for males to put more resources into whatever raises reproductive success, and less into body maintenance, than females. This is actually compatible with (1), as growing bigger probably raises reproductive success at peak health.

  19. 19
    Jadehawk

    wish we could disentangle the potential effects of this from the cultural ones, i.e. the “toxic masculinity” behavior that goes beyond being youthfully reckless; men and women still have diet differences, different rates of preventive doctor visits, etc.

  20. 20
    strange gods before me ॐ

    Rev. BigDumbChimp, yep it’s Randy Stimpson, and he’s not banned from FtB Pharyngula, yet.

  21. 21
    Nerd of Redhead, Dances OM Trolls

    Rev. BigDumbChimp, yep it’s Randy Stimpson, and he’s not banned from FtB Pharyngula, yet.

    Ah, RS. That explains the stupidity and the attitude. Still waiting for scientific evidence for his imaginary creator/designer. I’ll probably die waiting for that evidence….

  22. 22
    zekehoskin

    It’s not completely accurate to say that natural selection can’t have an effect on male-affecting mitochondrial genes. Having a living maternal grandfather might make it more likely for a woman’s daughters to survive.

    Cue Robert Heinlein’s concept of a foundation that bribes people to reproduce if their ancestors lived long enough.

  23. 23
    Amphiox

    I wonder how this effects species without genetic sex determination? Actually that would be a good test – you would expect that if mito-nuclear conflicts are the cause of male biased senescence that it would be absent in those species.

    I don’t think that would work. The male is pretty much definitionally the sex that produces the small, motile gamete, while the female is the one that produces the large, sessile gamete. And even without specific mitochondrial exclusion, this results in the majority of the mitchondria coming from the female gamete, simply due to size and dilution factors.

    Even without genetic sex determination, the majority of mitochondria will be inherited from the female parent’s gamete, and there will still be the issue of interplay between mitochondrial genes and the male-specific gene expression.

    What you would need is to find a species without differentiation in mitochondrial inheritance, a species whose gametes are more symmetric. But AFAIK, all such examples are unicellular.

  24. 24
    crowepps

    left0ver1under @ #5 – “To me it looks like the greater number of males makes up for the shorter life span, nature’s way of equalling out the genders over time.”

    In determining ‘natura l’ sex ratios, it would also be necessary to factor in the ‘natural’ maternal death rate of about 1 in a hundred women.

  25. 25
    qwerty

    My mother’s curse is to take care of my 97 year-old mother.

    Dad lived to the ripe old age of 89; so, I suppose that bodes well for me.

  26. 26
    john3141592

    My first thought was that my riskiest behavior as a youth was turning nineteen in 1963 but, really, only 52,000 men died in Viet Nam, and that’s a tiny percentage of the population.

    Going to the Air Force Academy for a year was riskier, but I took very early retirement (after one year) and dodged that bullet.

    Taking ROTC classes in college to try to get out of Reserve meetings didn’t work and could have been risky in the end, but I quit that and then refused a special recruiter’s offer to give me a commission anyway and send me to flight school. The Air Force is the branch of the service where they shoot the officers rather than the enlisted men.

    All of which is a roundabout way of saying that I suspect that, for American men, death in war is not a big risk overall.

  27. 27
    LykeX

    Dad lived to the ripe old age of 89; so, I suppose that bodes well for me.

    Well, that’s the question, isn’t it. Since you, by definition, don’t share your father’s mitochondrial DNA, even if he was lucky enough that there was no nuclear-mitochondrial conflicts, you can’t be sure that the same is the case for you. That’s the point of there being no paternal inheritance of mitochondria.

  28. 28
    Holms

    1) It’s down to size. Smaller people live longer, and women are on average smaller than men. It would be interesting to look at species where females are larger – are they still longer-lived?

    Quite frequently, yes.

  29. 29
    Rev. BigDumbChimp

    Rev. BigDumbChimp, yep it’s Randy Stimpson, and he’s not banned from FtB Pharyngula, yet.

    That’s right. I had forgotten his name.

  30. 30
    Naked Bunny with a Whip

    I thought it was because women steal our pineal gland secretions.

  31. 31
    hemlock

    If earlier death is something that actually is a guy thing, then you’d expect the average life expectancy gap to stay pretty static (all things being equal) but we’re not seeing that. The gap in life expectancy has steadily narrowed in developed nations, while women are still making modest gains, men are gaining at a greater rate. This is thought to be because of improved treatment of heart disease which was/is a major killer in middle age, more men not smoking, less men working in heavy industry and so on.

    This could have the effect if the trend continues for life expectancies to converge e.g. “What’s interesting at the moment is that in the last 20 years or so, male life expectancy at 30 has jumped by about six years and if it jumps by the same amount in the next 20 years it will converge with female life expectancy.” http://www.bbc.co.uk/news/health-17811732 or “Women may tend to live longer than men but they lag behind them when it comes to gains in life expectancy, according to a new nationwide study from the Institute for Health Metrics and Evaluation (IHME). The study analyzed county-by-county data from 1989 to 2009. In that time period, life expectancy for men improved by an average of 4.6 years – but for women, it improved by only 2.7 years.” http://www.cbsnews.com/8301-504763_162-57418059-10391704/women-lag-behind-men-in-life-expectancy-gains-study/

    Historically (and without modern medical interventions of any type) it was men that lived longest – this paper covers this and says “Historically, the male tended to survive longer than the female, a situation that appears to have persisted from the origins of our species until well into the modern era. The great risks associated with childbirth since antiquity began to be overcome as aresult of medical advances on a broad front, improvements in midwifery, and rising social status of women in general.” http://www.soa.org/library/research/transactions…/tsa89v414.pdf

    Very possibly men do age faster than women and this is genetically mediated, but looking at the stats I can’t help thinking that while this may apply it’s obviously overwhelmed by other factors, such as the risks of death in childbirth in women or heart disease in men as well as behaviours such as smoking that tend to decrease overall life expectancy.

  32. 32
    David Marjanović

    To me it looks like the greater number of males makes up for the shorter life span, nature’s way of equalling out the genders over time.

    But why equal them out, and why do so long after menopause???

    I remember, a few decades a go the claim was that the difference was simply more men smoke than women, thus non-smokers live the same length. I really don’t think that claim holds true anymore. (do more men smoke than women, still?)

    Yes, and the same holds for booze, and both have an effect, see comment 19; it’s just, apparently, not quite the whole story.

    there’s a significant amount of information shuttling back and forth between the nucleus and the mitochondrion

    Please define information.

    In this case, what it all means is the fact that most mitochondrial proteins are coded by the nuclear DNA, not by the mtDNA, and that the mitochondrial metabolism triggers all sorts of gene regulation in the nucleus by changing how abundant stuff is in the cell.

  33. 33
    alwayscurious

    Very possibly men do age faster than women and this is genetically mediated, but looking at the stats I can’t help thinking that while this may apply it’s obviously overwhelmed by other factors, such as the risks of death in childbirth in women or heart disease in men as well as behaviours such as smoking that tend to decrease overall life expectancy.

    This seems reasonable on the face of it, except that male/female life expectancy disparities show up across all cuts of the population: whether you start at age 0, 20, or 40. Females still outlive males, even after childbearing, smoking, drinking & risky teenage behavior is factored out. This isn’t entirely unexpected though, sex-based life expectancy differences are seen across many species of mammals. There are some thoughts floating around about steroids’ effect on aging could explain part of this disparity. For example, estradiol appears to have some neuroprotective effects and some neurologists hope it will unlock secrets to neurodegenerative diseases (which strike males younger & more often than females). So if the male-female gap is closing, I think that’s more a testament to how much more money & interest society puts into studying men’s health problems than women’s.

  34. 34
    zekehoskin

    My error. Edit “living maternal grandfather” to “living uncles on her mother’s side”. Or great-uncles on her maternal grandmother’s side. Or brothers, or maternal half-brothers, or male cousins from her mother’s sisters. In general, male relatives descended in a strictly female line from any strictly female ancestor would presumably have the same mitochondrial DNA. All interacting with different nuclear DNA, of course . . .

  35. 35
    flyonwall

    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.

    Perhaps, but can’t there be selection to fine tune the nuclear genome to the mitochondria?

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