Elsevier

Medical Hypotheses

Volume 62, Issue 1, January 2004, Pages 151-154
Medical Hypotheses

Tying it all together: telomeres, sexual size dimorphism and the gender gap in life expectancy

https://doi.org/10.1016/S0306-9877(03)00316-5Get rights and content

Abstract

The classic explanation that women outlive men solely due to hormonal and lifestyle differences, does not withstand a critical analysis. In developed countries, the average gap in life expectancy between the sexes is 7 years. It has widened over the last decades, despite the trend of women copying the ‘unhealthy’ lifestyle of men. Estrogen levels in postmenopausal women are virtually identical to estrogen levels in males and can hardly explain the discrepancy. Furthermore, testosterone got its bad reputation from one study on mentally retarded men, which has to be interpreted with caution. However, sexual size dimorphism with men being the larger sex in conjunction with the limited replication potential of human somatic cells might account for higher mortality rates in males, especially at old age. The hypothesis, as presented here, is based on the well-known concept of a cellular mitotic clock, which was discovered by Leonard Hayflick almost half a century ago. The underlying counting mechanism, namely the gradual erosion of chromosome ends (telomeres) due to the end replication problem of linear DNA molecules, was first described by Alexey Olovnikov in 1971 and with minor modifications has become a widely accepted paradigm. In a recent Lancet study, an inverse correlation between mean telomere length and mortality in people has been found. In this and two other studies, it was confirmed that males do have shorter telomeres than females at the same age. This is almost certainly a consequence of men being usually taller than women, although nobody has done an investigation yet. Clearly, a larger body requires more cell doublings, especially due to the ongoing regeneration of tissues over a lifetime. Accordingly, the replicative history of male cells might be longer than that of female cells, resulting in the exhaustion of the regeneration potential and the early onset of age-associated diseases predominantly in large-bodied males. Inherited telomere length variation between unrelated individuals might have obscured a clear correlation between body height and mortality, leading to conflicting results in some studies. Finally, I propose that the secular height increase over the last decades, of about 2.5 cm per generation in the western world, has to be blamed for the widening of the gender gap in life expectancy.

Introduction

The worldwide phenomenon of higher life expectancy for women, although generally acknowledged, is still an unsolved puzzle. In 1998, according to the US Census Bureau, the average gap in life expectancy at birth between the sexes was 7 years in developed countries and 3 years in developing countries [1]. Even though more boys than girls are born in all countries, middle-aged women start to outnumber men and the female advantage increases with age.

While risky behavior, unhealthy lifestyle (alcohol, tobacco) and hormonal differences might have contributed to higher male mortality rates, they cannot entirely explain the phenomenon. Risky behavior in males for example cannot account for the discrepancy of mortality rates beyond the age of 60, but at that point men are twice as likely to die as women [2], mainly due to cardiovascular disease and cancer [1]. In addition, women have been increasingly adopting the ‘unhealthy’ lifestyle of men in the last 40 years or so, but in most developed countries the gender gap has still widened [1]. This leaves us with the hormonal differences. In 1969, Hamilton published data about the median life span of castrated men in comparison to intact men (although mentally ill), who were inmates at the same hospital. He found a 13.6 year difference in lifespan [3]. Paradoxically, median lifespan in the control group was very low. A median life span of 55.7 years, as reported in this paper, would match the known data of that time, if it were life span at birth, but Hamilton collected his data from a preselected group. After all the participants must have reached a certain age to become inmates at a hospital for mentally retarded. Since infant and early childhood mortality was still incredibly high during that time, median life span is expected to be much higher in this preselected group. So the only thing he proved was that testicular hormones are particularly harmful to mentally retarded men incarcerated in US state mental hospitals in the early 20th century. Nevertheless, testosterone has been regarded as a ‘killer’ since. Although, a study on biographical data of castrated singers compared to intact male singers born between 1581 and 1858 did not reveal any significant difference in mean life span. These data published in Nature in 1993 show that prepubertal removal of the testes had no influence on the longevity of men [4].

In contrast to the allegedly unhealthy testosterone, estrogen is generally considered as life prolonging. But even if estrogen would have a positive impact on life expectancy, estrogen levels in postmenopausal women are on a record low, comparable to estrogen levels in males. It is hard to imagine that a hormone increases life expectancy, if it is virtually absent during the last 30 years of a woman’s lifetime.

Another theory on the cause of the gender gap is based on the random inactivation of one X chromosome in female cells [5]. For X-linked diseases it has been known that having two X chromosomes provides a health advantage [5]. Since it is very unlikely that mutations in genes on the X chromosome are involved in all age-related diseases and that mutated versions of these genes occur in all men, this model might be of academic value only.

Section snippets

The hypothesis

Clearly, to solve the puzzle, we have to look for other gender-specific differences. Like the gender gap, sexual size dimorphism (SSD) with men being the larger sex is a worldwide phenomenon. In mammals, a strong positive correlation between SSD and male-biased mortality has been reported [6]. The authors of a research article, recently published in Science [7], linked large body size to a higher burden of parasitism, resulting in increased mortality rates due to infectious diseases. However,

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