14 August 2017: 

In this ageing world, the field of the 'epidemiology of longevity' has been expanding rapidly in recent years. With a dramatic increase in survival rate to advanced old age over the past century, longevity can be described as an epidemic. Many studies have evaluated the impact of factors such as low socioeconomics in childhood, genetics, environmental, dietary and lifestyle (smoking and alcohol use), which negatively affect longevity. Although mortality rates for females are lower at each age than those of men, a close association between reproductive characteristics and longevity was recently documented. 

Several reproductive factors, such as the age at first birth, parity and age of menopause, have been found to be associated with women's longevity. The recent prospective (WHI) study, in a large multi-ethnic cohort of postmenopausal women, examined 20,248 women from 40 clinical centers (aged 50–79 years, mean age at baseline 74.6 years); 10,909 (54%) of these women survived to age 90 years [1]. The odds of longevity were significantly higher in women with later age at first childbirth (adjusted odds ratio 1.11; 95% confidence interval 1.02–1.21 for age 25 years or older vs. younger than 25 years; p for trend = 0.04). Among parous women, the relationship between parity and longevity was significant among White but not Black women, while women with two to four term pregnancies compared with one term pregnancy had higher odds of longevity. This long-term, follow-up study reported that a rising number of pregnancies were associated with higher likelihood of longevity in the participants who survived to the age of 90 years. It was pointed that this was independent of demographic characteristics, socioeconomic position, lifestyle behaviors, reproductive factors and health-related factors. Despite these strengths, the authors pointed at a limitation of the study: women included in this study were on average aged 75 years at enrolment and may have had a higher likelihood of achieving longevity as they had already survived to their seventies. Also, with respect to historical events, participants may have had different experiences that may have influenced their life expectancy. So, because of potential selection bias, this cannot be applicable to the general population of childbearing women.

Earlier, another prospective study investigated associations between reproductive factors and survival to age 90 years in postmenopausal women. The Women's Health Initiative recruited women from 1993 to 1998 and followed them until the last outcomes evaluation on August 29, 2014 [2]. The study included 16,251 women (average age 74.7 years, range 69–81 years) for whom survival to age 90 during follow-up was ascertained. Women were classified as having survived to age 90 (exceptional longevity) or died before age 90 years. Researchers evaluated the associations of ages at menarche and menopause (natural or surgical) and reproductive lifespan with longevity, adjusting for demographic, lifestyle, and reproductive characteristics. It was observed that in total 8892 (55%) women survived to age 90. Women aged at least 12 years at menarche had modestly increased odds of longevity (odds ratio (OR) 1.09; 95% CI 1.00–1.19). The data suggested a significant trend toward increased longevity for those with later age at menopause (natural or surgical; ptrend  =  0.01), with ORs of 1.19 (95% CI 1.04–1.36) and 1.18 (95% CI 1.02–1.36) for age at menopause of 50–54 years and at least 55 years compared with less than 40 years, respectively. Later age at natural menopause as a separate exposure was also significantly associated with increased longevity (ptrend  =  0.02). Researchers stated that a longer reproductive lifespan was significantly associated with increased longevity (ptrend  =  0.008). The odds of longevity were 13% (OR 1.13, 95% CI 1.03––1.25) higher in women with more than 40 compared with less than 33 reproductive years. The authors concluded that reproductive characteristics were associated with late-age survival in older women. After loss of reproductive capacity (fecundity), humans enter a prolonged period of senescence. Significant correlation between late age of natural menopause and longevity further encourages future research in this area [2].

The above-mentioned data and research suggest some associated questions. First, do women who achieve exceptional longevity reproduce later in life? Evolving trends of a relationship between later childbearing and health outcomes or post-reproductive survival have attracted much attention but have not been extensively studied. Extension of post-reproductive life expectancy has been found to be associated with late age at first childbirth. It is well documented that delayed childbearing affects the health risk of older women (40 years or more) and their infants. However, positive outcomes of elderly pregnancies may be an indicator of present good overall health and can predict the women's future longevity. Review of currently available literature infers that avenues for further research in this area should be initiated and/or pursued [3]. The ability to deliver successfully at an older age may be associated with later age of menopause [4]. Retrospectively, women with late onset of menopause have been found to have better nutrition, less stress and higher socioeconomic position in childhood, which probably influence their behavior and overall health in adulthood. Several factors may explain the association between later age at first childbirth and longevity. The average maternal age at first childbirth is rising dramatically and fertility rates are declining [5]. Overall, it appears that age at last childbirth routinely correlates with post-reproductive longevity and slows senescence in late fertile women.

Second, can this have any public health implications? Epidemiologic studies of longevity are likely to have enormous implications for ageing and public health. Over the past two decades, age at first birth has risen for all races and those of Hispanic origin. This changing trend has an important impact on population structure such as lower total fertility and family size. The correlation associated with older maternal age/late reproduction and longevity does not imply that intentionally one should delay childbearing, because of complications associated with older maternal age. Furthermore, although parity was positively associated with longevity, increasing parity was associated with a decreasing trend for the odds of longevity. More research is warranted to determine the association of the modifiable and social factors with age at first childbirth and parity with longevity, which is quite challenging. On another matter, a longer reproductive period and advanced age at menopause have been shown to be significantly associated with better cognitive performance or lower rate of cognitive decline. This indirectly supports a link between hormone deficiency and cognitive ageing, but no meta-analysis report is yet available [6].

Comment

The age of 85 years is often used to define the oldest old but there is no single accepted age threshold for longevity. Persons achieving an age of 90 or more years remain overwhelmingly White, at 88.1%, with African Americans making up 7.6% and Asians 2.2% of the over-90 population. Several long-term cohort studies have followed older adults long enough to identify the most long-lived and to define many factors that lead to a long lifespan [7]. Female life expectancy is increasing globally in this century, by more than 25-30 years in developed countries, and women live longer than men, on average [8].

Currently, a female life expectancy advantage is nearly universal, except in some southern Asian and sub-Saharan African societies where cultural factors (low female social status and stronger preference for male offspring) predominate. Women have better survival at every age and thus appear to be more robust, rather than ageing more slowly [9]. This assumption is justified as human reproductive senescence occurs much faster than somatic ageing and females exhibit prolonged post-reproductive lifespans (PRLSs). Determining the factors that influence and mechanisms that underpin PRLSs has proved a significant challenge. Many classic and modern hypotheses propose to explain PRLSs and discuss their application in humans [10]. The disposable soma theory of ageing argues that investment in reproduction deprives organisms of resources required for self-maintenance, thus reducing longevity. This effect might be more easily explained in females of developing countries, through the direct physical burdens of pregnancy, childbirth and breastfeeding. The Reproductive Cell Theory of ageing maintains that hormones which promote growth and development early in life, to achieve reproductive maturity, act later in an antagonistic pleiotropic manner, promoting senescence. A genetic predisposition to hinder and/or delay these hormonal mechanisms might reduce reproductive success and at the same time delay ageing and mortality in women and men alike [11-13].

It is important to note that there is already robust evidence that reproductive events are associated with women's longevity; however, reproductive longevity has not increased over the same period of time. The association of age at childbirth with all-cause mortality has been inconsistent. Data on a woman's childbearing history and her later health and mortality correlation indicate that, on reaching midlife and controlling for early and later socioeconomic status, first birth before age 20 is associated with a hazard of early death [14].

In conclusion, current efforts to find clear information on the association of reproductive characteristics with late-age survival/life expectancy can help to identify targets for future public health interventions in the area of pre-conception and family planning counselling, thereby improving their healthy longevity in the long term. However, future studies to identify genetic factors in reproductive fitness, rate of ageing and age-related conditions are advocated for deeper understanding of underlying biological pathways. There is a clear need for more prospective studies with large numbers of exceptional survivors to determine the relationship between age at childbirth and survival to extreme old age. There is much work to be undertaken in this area.

Sunila Khandelwal

Senior Consultant Gynaecologist, Fortis Escort Hospital, Jaipur, India

References

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