Next month I turn quinquagenarian. And try as I might to resist the significance that so many people (confusingly to me) attach to anniversaries with a ‘0’ on the end of them, and the social networking-driven general trend for looking back and collecting friends like badges, I have to confess to a degree of, err… taking stock? I am, I consider, generally pretty fit and healthy. An assessment a couple of years back scored me as having a high level of fitness for my age (“Young man!”), and put me in the low risk category for diabetes and cardiovascular disease in the next ten years. However, I am, admittedly, not as fit as I could (perhaps ought to) be. And it is now undeniable that middle-age deterioration has well and truly set in.
I recently collected new glasses: separate pairs for distance and reading, after a re-test confirmed a new prescription (that I was aware had become necessary). I have a problem with my left elbow, reminiscent of a stress or impact injury, though I don’t recollect any such. Since returning last year from Argentina and lengthy drives between beef and Malbec-fuelled stopovers, with my meat-yanked crown in my luggage for subsequent re-cementing by my dentist (who I don’t need to tell me that my teeth are further apart than they used to be), I am struggling to shift the extra stone I amassed. This is despite regular running, but in replacement-requiring trainers, with a consequent bruised coccyx to go with the occasionally recurring, football-legacied, posture-distorting lower back pain.
(Probably coincidental, and so perhaps nothing to do with ageing… ) whilst the long-standing seborrhoeic keratosis on my back is okay where it is, in the last few (~ six) years, I’ve had removed an apocrine hydrocystoma by my right ear, and a pyogenic granuloma from my left thumb. I’ve suffered two serious bouts of influenza, which I’d previously managed to avoid/resist for twenty years, such that I now (perhaps irrationally) seek the annual vaccine. And, despite temporarily effective functional endoscopic sinus surgery in 2007, I am susceptible to recurring acute exacerbation of chronic rhinosinusitis, which has me prone to random stuffy headaches that (and I’m not exaggerating) can ruin a day.
And then there’s the broken handle on my mug of time. And my increasing befuddlement by a royally distracted nation’s squealing fascination with a prince’s caroms (“It would have been perverse not to publish them” !?! Get that for rationalisation.), with even Newsnight (I suppose in order to fill the gaps left by the repeatedly spurned invitations to questionably inept government ministers) resorting to garnering the opinions of over-audible narcissists.
Then, as if that is not enough, I learnt last week that my sperms are riddled with mutations!
Actually, I kind of already ‘knew’ this. I was told so by a lecturer in 1996, back in the days when I could call myself a geneticist, before I became cytologically cornered. Replication is an error-borne process, so it makes perfect sense that, over time, mutations accumulate. And more rapidly so in continuously replicating cells. But I was younger then, so interest was more academic than personal. But now I’m older – and there it is. Official. In Nature. Coming under one of the media’s sure-selling headline categories – Sex – this was a story liable to sensationalism (“You mean like the title of this post, Lee?”). Well, let’s ignore the alarmists and look at the paper. Are the unmediated facts – particularly the rate of mutation; and the already recognised link between paternal age and increased risk to offspring of diseases such as schizophrenia and autism spectrum disorder (ASD) – so alarming?
Kong et al studied mutation rates by high coverage, whole-genome sequencing of 78 Icelandic parent–offspring trios. Iceland’s relatively recent transition from rural agricultural to urban industrial way of life begat a steep fall in the average age of procreating fathers (from 34.9 down to 27.9 years between 1900 and 1980). But by 2011, associative improved education and access to contraception saw this rise back up to 33.0 years. Confirmed here is the effect on the rate of genome-wide de novo mutations wrought by these demographic fluctuations in male procreative age. This, and prior epidemiological and other studies linking de novo mutations to schizophrenia or ASD, indicate that the age-dependent increase of sperm-borne de novo mutations proportionally increases the risk of siring children with susceptibility to such disorders.
As the very useful accompanying online ‘News & Views’ piece contextually informs, the brain is the highest scoring organ for number of genes expressed. Whilst mothers transmit a fairly constant, age-independent number (around fifteen) of de novo mutations, an estimated average of 2.01 mutations per additional paternal year increases the higher number transmitted by fathers. Kong et al‘s estimated rate increase corresponds to the number of paternally transmitted de novo mutations doubling every 16.5 years, and increasing eight-fold over 50 years. Hence, paternal age is the dominant factor in determining the number of de novo mutations in a population’s children, and correlates with the increased incidence of multifactorial disorders of brain function in those populations.
It was suggested by the author of that ‘News & Views’ piece that, because most mutations are deleterious (– For some reason, I thought most were neutral? –), young men now might want to consider having a sample of their sperm frozen in case they find they want to reproduce later in life; and moreover, that freezing young men’s sperm might be beneficial to public health in limiting the rate of deterioration of the gene pool in human populations subjected to selection pressures relaxed by increased living and educational standards, and consequent increased longevity. (Question – is the waning of libido with age an evolutionary stable strategy? To limit the transmission of deleterious mutations?) This thus suggests that those populations with high mortality and lower life expectancy have a fitter gene pool, but which is hindered in conferring (material) advantage due to their lacking the power and wealth enjoyed by those longevous, selection-relaxed populations.
Sighhhh. Scientists, eh! Telling us things we don’t want to hear. Although I am off the scale of the 18 to 40.5 predominant age range of this study’s fathers, such that ‘… more data at the upper age range are needed to evaluate the nature of the acceleration better…’ that does not really make me feel better. The trend seems pretty solid. Why can’t I be like a populist politician and just ignore vote-jeopardising evidence? Well, I don’t want to read of those individuals who sired in their (a)trophied dotage, because anecdotes (dis)prove nothing. And I don’t want to be told that I should have had a sample of my sperm frozen in my twenties. Because, I was a different person then. (Thanks, Alice.) It would, would it not, be somewhat akin to consenting to someone you used to know being the surrogate father of your child? (I used ‘akin’ in there because I thought it kind of worked.) Moreover, someone your now partner probably never knew. Not that any decision to store-freeze sperm (or eggs) is anything I object to in principle: there are instances where the consented recourse to prior frozen gametes are entirely valid, and their ethical naysayers do not much interest me. But if I’m still available, and functioning, and still manufacturing the stuff in my out-built 2°C-cooler manufactories, then personally I’d prefer to run with contemporary rather than retrospective ejaculate.
Selfish? Well, that’s often men for you. Who need reminder that it is not entirely about their preferences. And, considering the tug-of-war pressurisation applied to women and when they have children, maybe it’s about time men were slapped round the face with the wet fish of reality for once. We really shouldn’t whine. Particularly as we’re looking at an increased risk – of an already small risk. And is this necessarily all negative? I should stress here that I’m not in any way flippantly denigrating (in the manner of a disRespectful, rape-fractionating Republican) those afflicted with the disorders discussed. I mean at the population level. Because it is on populations that evolution, which doesn’t give a damn about individuals, operates. This trend may well increase the prevalent risk of certain disorders. But haven’t the underlying gene variants been naturally selected… because they are also those highly associated with higher creativity? (Question – if increased incidence of schizophrenia and ASD correlate with increased paternal age, does an accompanying increased incidence of heightened creativity also become apparent?) That which pervades the arts, enriches culture… and catalyses ground-breaking science? This might argue, then, that describing ‘deterioration’ of the human gene pool is debatable.
So, being past my physical prime, I realise also that gone is the time when I might have had a great scientific idea of my own. But should I really, for public health concerns, maintain my hitherto childlessness? Or take the small (ever-present, regardless) risk? And perhaps console myself in speculating that maybe I’m of a vintage with an increased ‘chance’ (randomly acquired) of procreating a potential future genius? One who might contribute to the discovery and development of effective treatments and cures for these complex disorders. Or the alleviation of the plight of those populations that aren’t so fortunate to live as long as we amorous codgers
- Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, Gudjonsson SA, Sigurdsson A, Jonasdottir A, Jonasdottir A, Wong WS, Sigurdsson G, Walters GB, Steinberg S, Helgason H, Thorleifsson G, Gudbjartsson DF, Helgason A, Magnusson OT, Thorsteinsdottir U, & Stefansson K (2012). Rate of de novo mutations and the importance of father’s age to disease risk. Nature, 488 (7412), 471-5 PMID: 22914163