Sleep, Genetic Conflict, and Human Longevity

Telomeres are repeating sequences of DNA found at the ends of chromosomes that protect DNA strands on the chromosomes, thus reducing chances for harmful mutations. One of the most frequent ways to get a harmful mutation is by losing pieces of information from each end of the chromosomal strand. Each time the DNA makes a copy of itself, its telomeres get shorter, thus increasing chances that information will be lost through the ends of the strand. The telomeric caps at the ends of the strands prevent this loss of information and therefore prevent accumulation of mutations over time. The longer the telomeric cap, the longer the individual will be protected against mutational accumulation and therefore, theoretically, the longer he or she will live. In sum, short teleomeres increase chances for mutation accumulation over time because they eventually will wear away to nothing while longer telomeres protect against this effect. (Aviv and Susser, 2013).

But there is a major exception to this telomere shortening effect: sperm. In fact, the telomeres in sperm-producing stem cells not only resist wearing away, they actually grow. This growth may be due to the fact that sperm are bathed in the telomere-repairing enzyme telomerase. Thus, the older the man, the longer the telomeres in his sperm will be.

But that’s not all: a really stunning finding in recent years demonstrated that this telomere lengthening effect in sperm of older men can be passed on along the paternal line from father to son and grandson (Eisenberg et al., 2012). Therefore, the age at which a man conceives his offspring could theoretically increase that offspring’s chances to live a long life and increase his (and the whole lineage’s) reproductive fitness.

But wait a minute! You might be asking yourself “What about all those studies that show deleterious effects of older paternal age on offspring?” Older Dads tend to have kids with greater health risks of all kinds right?

Yes and No. Some studies show negative effects of paternal age on offspring while other studies show positive effects (Janecka et al., 2017). Advancing age of the mother certainly is associated with negative effects on offspring but less so for the Dad-though there is no doubt that some negative effects are there and well documented. Aging is associated with de novo mutations and thus you get the association between parental age and offspring defects. Nonetheless, this negative effect of aged parents on offspring is diluted or muted for older Dads with longer telomere lengths and I predict that deleterious effects will be especially muted for boys vs girls. The issue is exceedingly complex as the effects of paternal age on offspring are likely mediated by many factors from age of the mother, birth order effects in the family and economic status of the Dad. Most importantly however is that effects of paternal age on offspring should differ as a function of gender of offspring. Effects (both negative and positive) of paternal age on offspring are likely to be gender specific simply because (as noted above) telomere length is inherited down the paternal line.

But what does all this have to do with sleep? First it has been demonstrated that both too much sleep and too little sleep is associated with short telomere length (Jackowska et al (2012). You need optimal sleep amounts in order to have longer telomere length. Interestingly, the same holds true for semen quality: you need optimal sleep amounts for optimal semen quality (Chen et al., 2016). Too much or too little sleep will result in reduction in semen counts and quality in a dose response manner. It is possible that the effects of restricted sleep durations on semen quality is related to sleep effects on telomere length. In any case, non-optimal sleep duration carries a higher fitness cost for males than for females given that semen quality and telomere length declines after non-optimal sleep.

So, we know the following: 1) telomere length may increase longevity and fitness via protection against harmful mutations; 2) sperm is protected against short telomeres and is associated with growth in telomere lengths; 3) telomere length can be inherited down the paternal line from an older Dad, 4) you need optimal sleep durations in order to have longer telomere lengths and better sperm quality.

Now I caution the reader that all 4 of these claims are contested in the scientific literature. They are not yet established facts. My personal opinion is that they will be established facts soon. Thus, we need an explanation as to how these 4 facts hang together and what it all means for a theory of sleep function.

Here is where Eisenberg and Kuzawa’s (2011; 2013) work on the evolutionary theory of paternal age effects is so useful. In order to optimize reproductive fitness, parents need their kids to be prepared for whatever environment they find themselves in. If it is a chaotic environment then the best strategy for parents and kids is for the kids to grow up fast and reproduce fast. The fast schedule results in shorter lifespans. You live fast and die young. If, on the other hand, the environment is more stable, then the optimal reproductive strategy is to grow more slowly and reproduce later in life. In this scenario offspring will tend to live longer. But for this slower strategy to work parents need to know about environments in the future—when their kids will be born and growing into their maturity. The parents (and kids) need to use currently available information to make bets on how the future will turn out. But how can potential parents (or growing kids) peer into the future? What information can parents and kids use now to plan for the future?

Now what Eisenberg et al suggested is that paternal age at reproduction is a very reliable signal of environmental stability. If you have men who are living into older age brackets and reproducing at those ages, then that is a very good evidence that things are stable enough to support slower growth and reproductive schedules. Now we note the crucial point in all of this theorizing: Only certain kids will be able to use the information about older Dads. Only the boys (and to some extent the girls) born to older Dads have the information in their genome (in the form of long telomeres) that tell them what the environment is likely to be like when their children will be born. They therefore have extremely valuable fitness-related information no-one else in the group will have. As Eisenberg and Kuzawa (2013) put it (p. 2): “Thus, the lineages of men with the ability to extend sperm telomere lengths with age and to transmit these modified telomeres to offspring might have increased Darwinian fitness because their offspring were better able to calibrate their reproductive and maintenance expenditures across the likely duration of their lifespans within the variable environments that human populations have confronted.”

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The offspring of older dads will have in their genomes the information concerning long term stability of the environments that will allow those kids to plan optimally for the future, and thus increase their fitness. While receiving the “long telomeric inheritance” signals optimism for these kids, we have seen above that restricted sleep amounts will partially negate these beneficial effects—especially for males. As mentioned above, non-optimal sleep duration carries a higher fitness cost for males than for females given that semen quality and telomere length declines after non-optimal sleep. Why the differential effect on males?

We come now to the last step in my argument about sleep and longevity. No-one knows the answer to this question. Therefore I feel free to suggest a possibility. In my 2004 book on REM sleep I argued that sleep amounts were subject to influence of genetic conflict mediated by imprinted genes with maternal line imprinted loci favoring long sleep durations and paternal line genes favoring shorter sleep durations. Within this theoretical framework it is in the interest of maternal line genes to promote non-optimal and especially longer sleep durations. We have seen that non-optimal sleep durations exact a differential cost on paternal line telomeric function. There is increasing evidence that teleomere length is associated with enriched DNA methylation levels within imprinted loci (Buxton et al., 2014). Within this theoretical frame therefore both sleep duration and human longevity itself is a bit of a battleground in the eternal war fought between the sexes.

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