Biological determinants of the gender gap in life expectancy. − Rakyat Biologi

Many analysts of human life expectancy believe that though cultural factors are obviously important, there is a substantial biological basis for women's advantage in life expectancy. The life expectancy advantage of females seems to be characteristic of many species, but the data available most often does not comprise longitudinal follow-up of individuals to death. In other words, indications are indirect. In laboratory animals, neither sex seems to have an advantage in longevity. Then again, laboratory conditions favor the male sex, because the male sex's weaker immune system is minimally challenged in such an aseptic environment. Several investigations have shown that laboratory rats and mice are more susceptible to infection and death when exposed to controlled doses of viruses or bacteria. For example, the possible site of expression of the sex difference in susceptibility to infection with Strongyloides ratti (a parasite) was studied in C57BL/6 mice. The intensity of infection, measured by daily larval output in faeces or by intestinal worm burden, was significantly higher in males than in females. This sex difference was already expressed during the migration of larvae from the site of subcutaneous inoculation to the cranial cavity or lung as early as 24 h after infection. Conversely, there was no significant difference in the larval output in faeces or in the worm burden of male or female recipients after implantation of adult worms using a stomach tube. When the susceptibility to infection with S. ratti of gonadectomized animals was examined, the daily larval output in faeces of orchidectomized males was significantly reduced to the level of intact females, while ovariectomy had no effect, suggesting that androgen is one of the important regulatory factors for the expression of sex difference. In fact, testosterone treatment of orchidectomized males or normal females could increase their susceptibility to or above the level of intact males. These results strongly suggest that sex difference in the susceptibility to infection with S. ratti in C57BL/6 mice is mediated by 'natural defence mechanisms' which are modulated by testosterone. The life threatening diseases whose prevalence is most influenced by gonadal hormones are infection, vascular disease and cancer. It is through its influence on these diseases that male castration has a life-enhancing effect in the few species so studied (rats, cats and humans).

Biological theory of life expectancy predicts that the gender gap ought not be the same in all types of species. The Gompertz law, dating back to 1860, states that the more monogamous species ought to have a gender gap in favor of females, whereas sexually promiscuous species ought to approach equal life expectancy. This prediction is based on the idea according to which fitness of genes has to do with the assurance of available resources, particularly food, for the individuals most fit, at any given time, to further the species. In other words, an animal will have a better chance of multigenerational posterity if at the moment he or she has a negative balance-sheet he or she dies. In monogamous animals, the male becomes "redundant" more quickly, according to this theory. Worse, redundancy is short lived. Biologically speaking, an individual is basically a reproductive asset, or a liability: an over-aged animal will at some point be consuming resources needed by its own progeny without contributing to the gene pool, thus defeating its own posterity. Of course, humans are relatively monogamous, like other supposedly monogamous species such as birds who also tend to cheat on their life-long mates. It took some pretty astute field work by scientists for this to be discovered by the way! So these species should, according to biological theory, have a gender difference in life expectancy. Humans are not the most sexually dimorphic of primates, but they are not the most monomorphic either. In fact, men weigh, on average, 15% more than women do. This directly affects, I think, in numerous ways, life expectancy. Larger specimens of a same species (especially the heavier ones) generally have a shorter life expectancy. And though it is risky to compare species with this scheme, it is less so to compare sexually compatible races. This can be done fruitfully with dogs. Small dog races have a longer life expectancy than large dog races. A McGill University researcher, Siegfried Hekimi has been studying and breeding worms (hematods) to gain understanding of the mechanisms of longevity. He has found differences between worms with short and long lives and he is now breeding the «short lifers» with «short lifers» and the «long lifers» with the «long lifers» so as to create pure races. The short-lived worms have higher basal metabolic rates, develop faster and become bigger. Hekimi has isolated four of the genes responsible for the race differences, but expects to find several more. He believes there are numerous systems involved which are controlled by various genes: cell division rates, resistence to different diseases, metabolic rate, etc. The particularities of short-lived hematods are reminiscent, to me, of general characteristics of males in sexually dimorphic species. As I will try to demonstrate in detail next, I believe that gonadal hormones modulate the function of many of these same systems found to correlate with life expectancy in genetic research such as that of Hekimi.

For the first million or so years of its existence, until the human species developed a relatively formalized and generalized public culture (ex: of hygiene, of medicine, of division of labor, etc.), life expectancy did not reach beyond the age of menopause and many women died during childbirth. I imagine that these primitive women must have been much more exposed to viruses and bacteria than were men (see chapter 7 for details). It seems to me that it was to the advantage of the species, in this context, for women reaching the age of procreation to develop, by natural selection, a certain robustness, particularly of the immune system, so that progeny could be cared for. Nature having limited resources, this advantage had to be paid for in suffering, namely by auto immune diseases, which without usually being fatal or preventing child care, really compromise the quality of life (especially life long after menopause, which as I have just explained, was not part of nature's plan). Perhaps to some extent because men ensured territorial integrity, repulsed predators, and hunted, they developed a greater muscle mass and strength, also by natural selection, which in turn required a special type of blood supply. Nature, having limited resources, might have made them pay a price for this advantage, namely heart and vascular disease. The idea according to which prolonged infant care by one parent makes longevity advantageous for the parent in question has recently been supported by a study comparing various species of monkeys. Among humans and other advanced primates, the sex that does more of the child-rearing tends to live longer, according to a study in the June issue of the Proceedings of the National Academy of Sciences. In species where mothers bear primary responsibility for childcare -- among humans and gorillas, for example -- females tend to have longer lifespans than males. But in species where fathers do as much or more of the child-rearing such as owl monkeys and titi monkeys -- males tend to live just as long or longer than females, according to Dr. John Allman, professor of biology at the California Institute of Technology in Pasadena, and colleagues. Analyzing survival data for 10 primate species, the researchers compared male and female lifespans, and looked at the relationship between lifespan and parenting role. In six of the species they studied -- humans, gorillas, orangutans, chimpanzees, gibbons, and spider monkeys -- females provide most or all of the childcare. In two species -- Goeldi's monkeys and siamangs -- the sexes spilt child-rearing responsibilities. Among another two -- titi monkeys and owl monkeys -- males take primary responsibility for carrying and caring for their offspring after birth. In general, the sex that provides more childcare tends to live longer, the researchers found. And the greater the difference in childcare responsibilities between the sexes, the greater the difference in longevity. "These results run counter to the reasonable expectation that the increased energy expenditure and risk of falling associated with carrying an infant would result in increased rather than decreased mortality," the authors acknowledge. But the trend makes sense from an evolutionary perspective, they point out. Higher primates usually give birth relatively infrequently, have just one offspring at a time, and give birth to young that need care for a relatively long time. Consequently, parents are more likely to produce offspring that survive long enough to reproduce themselves, if the caregiving sex lives longer. The bond between parent and child may also play a role in parental longevity, note the researchers. "It is conceivable that the strength of these bonds and their underlying neurochemical and hormonal bases might enhance survival," they write. "If there's a differential in care provided by father and mother, the sex providing for the care will be favored by natural selection, because their act is essential for the propagation of the species," Allman told Reuters Health in an interview.

Most of the biological factors favoring longevity of the female sex, in today's post-industrial societies, derive from steroid hormone sex differences. Longitudinal studies of men with unusual longevity (more than 80 years old) have revealed lower testosterone in the survivors, itself related to lipid and lipoprotein metabolism (metabolism of fat). Thinner people have significantly longer life expectancy. The life-preserving effects of post-menopausal estrogen include resistance to osteoporosis and subsequent hip injuries, and resistance to coronary heart disease. Though there are life-threatening effects of estrogen replacement therapy, including endometrial and breast cancer, these risk factors seem to be calculable from a woman's genealogy, and can be weighted into the decision, such that overall, we are looking ahead to an even greater chasm between the longevities of the two sexes, especially if we assume that smoking in women will reach a plateau soon. A recent multi-center large scale study found that post-menopausal estrogen replacement therapy prevented mortality by 17.4% in women without heart diseases at outset, and by a whopping 52.55 % in women with heart disease at outset ! Since only about 20% of North American women are now opting for estrogen replacement therapy, imagine the effect full conversion would have on life expectancy ! There seem to exist metabolic sex differences, in mammals, due to gonadal hormone action, which cause diffential risk for hypertension. For example, one study determined the effects of gonadectomy on the pathogenesis of hypertension. Male and female rats were gonadectomized at age three weeks. In intact rats, hypertension developed more rapidly and to a higher level in males than in females. By contrast, in gonadectomized rats, there was no sex difference in blood pressure because the development of hypertension was attenuated in males and exacerbated in females. None of these differences could be attributed to differences in either saline consumption or vasopressin release since no differences were found among the groups for either variable. Although the underlying mechanisms remain uncertain, the results of this investigation clearly show that the gonadal hormones affect the development of hypertension in the rat.

One could scrutinize the chain of events behind female longevity even further, and thus discover that risk factors in male mortality are not all hormonally mediated. Some are directly genetic. Because the human female has the XX gonosome pair and the human male the XY pair, the female is protected from bad genes by healthy genes on the allelic locus of the gonosomal counterpart. Male humans cannot inhibit bad genes located on the large X chromosome. These bad genes are responsible for countless nervous system disorders associated with mental deficiency. Worse, some of the X linked pathologies are lethal (Rett syndrome, Lesch Nyhan syndrome, etc.).

One outstanding sex difference in matters of health is that women are less satisfied about their health and men are more subject to life-threatening diseases. This apparent paradox invites some reflection. In industrialized countries, women consult doctors far more than men. It has been written hundreds of times that women simply complain more about, and consult doctors more, for their health problems. I believe this common attitude is not fair to women. The female predispositions for hysteria (which includes fabricated symptoms), hypochondria (imaginary disease) and somatization (exageration of symptoms) are far from sufficient to explain the higher medical consultation rate. One study investigated health problems of men and women in general medical practice. It found that so-called « psychosomatic » problems accounted for only 20% of the sex difference. I think one should also attribute some of the phenomenon to the types of diseases that women endure more frequently than men. Women are more subject to non-deadly chronic (long lasting and untreatable) inflammatory diseases (the auto immune diseases, see chapter 8), and to more subjectively painful psychiatric disorders such as depression. Men are more subject to diseases which they quickly recover from (infections for example) or which immediately kill them (cardiovascular disease for example).

In short, there seem to have existed evolutionary pressures for greater longevity of the female sex in humans and in several sepcies of monkeys and apes. The difference in life expectency seems to relate to genetic adaptations to the distinct ecological niche of each sex. To the extent that the males are specialized for aggressive action and the female for childcaring, then a sex differnce will be apparent, and it will be biologically fixed in that species. These genetic differentiations within a given species entail a cascade of biological and biosocial events operating through hormonal, neurochemical and even anatomical maturation, including, of course, in the brain.

The human male seems to be at a disadvantage for survival at all ages without exception, and biological factors seem to be invariably involved. I will cover the life span over four periods: prenatal, childhood, adolescence and senescence. I have decided to term the female advantage in life expectancy at these four ages the theory of the horseman of the four apocalypses, the horseman being the male specimen of our species. But before I get into these issues, it seems important for us to determine whether and how in humans one sex seems to get born more often than the other.