Interdisciplinary topics in gerontology最新文献

Adipose tissue accounts for approximately 20% (lean) to >50% (in extreme obesity) of body mass and is biologically active through its secretion of numerous peptides and release and storage of nutrients such as free fatty acids. Studies in rodents and humans have revealed that body fat distribution, including visceral fat (VF), subcutaneous (SC) fat and ectopic fat are critical for determining the risk posed by obesity. Specific depletion or expansion of the VF depot using genetic or surgical strategies in animal models has proven to have direct effects on metabolic characteristics and disease risk. In humans, there is compelling evidence that abdominal obesity most strongly predicts mortality risk, while in rats, surgical removal of VF improves mean and maximum life span. There is also growing evidence that fat deposition in ectopic depots such as skeletal muscle and liver can cause lipotoxicity and impair insulin action. Conversely, expansion of SC adipose tissue may confer protection from metabolic derangements by serving as a 'metabolic sink' to limit both systemic lipids and the accrual of visceral and ectopic fat. Treatments targeting the prevention of fat accrual in these harmful depots should be considered as a primary target for improving human health span and longevity.

Our understanding of gerontological bone loss and osteoporosis has grown substantially in the recent past. Clinical as well as basic and translational studies have been pivotal in providing us with the pathophysiology of this condition. They have also informed us of the various cellular and molecular mechanisms underlying age related bone loss. This chapter focuses on the current concepts and paradigms of age related bone loss in humans and how various animal and cellular models have broadened our understanding in this fascinating but complex area. Changes in hormonal, neuronal and biochemical cues with age and their effect on bone have been discussed. This chapter also outlines recent studies on the relationship between bone and fat in the marrow, and the fate of the marrow mesenchymal stromal cell population which can give rise to either bone forming osteoblasts or fat-forming adipocytic cells as a function of age.

This chapter presents data on the relations between reproduction and aging in both captive and free-ranging marmosets and tamarins. The relationship is examined from two perspectives. First, the relation of age to physiological impairments in reproductive function is explored. Callitrichid females, in common with many other nonhuman primates, begin to display anovulation associated with follicular depletion at a point relatively close to the maximum life span. Unlike Old World primates, however, they continued to display significant steroidogenic activity in the ovary. There are age effects on some reproductive output variables, such as litter size and inter-birth interval, though the effects are often small. Like other mammals, male marmosets display a change in levels of androgens with age, although the magnitude of the decrease is not large and they actually mount an elevated response to GnRH challenge as they age. We also examined whether age affects either the establishment or maintenance of a breeding position, the factors most important in determining lifetime reproductive success. Infant mortality did increase with increasing parturitions, suggesting that there may have been aging or parturition effects on lactation. Generally, marmoset females were well past the age of sexual maturity at the beginning of the tenure and approaching 8-9 years at the end of it. Reproductive decline did not appear to be a gradual process, but a rather abrupt one, often causing the dismantling of the group. There are potentially interesting relations among maternal age, mass and declining reproductive performance, given the known importance of mass as a determinant of reproductive success in female callitrichids.

New World monkeys have been used extensively as biomedical models for human diseases, yet little is known about aging in these animals. Life spans in cebids vary, with most species living to approximately 20-30 years of age. Capuchins may be an exception, possibly living as long as 40-50 years. Biomarkers of aging in squirrel monkeys have been studied primarily in relation to the reduced calorie model of aging. These data suggest that squirrel monkeys do not show the same physiological effects of aging as rhesus monkeys and they do not react to a reduced calorie diet the same as rhesus. Cebids are useful in several models of aging, including Alzheimer's disease and cardiomyopathy research. Reproduction in aging cebids has not been extensively studied, but it is known that aging squirrel monkey females experience a reduction in their reproductive potential after the age of twelve. Production of progesterone, estrogen, and bio-LH are all decreased in older squirrel monkey females. They are also prone to a condition similar to pelvic organ prolapse in aging human females. Taken all together very little is known about the reproductive function in aging New World monkeys.

Data from four Asian colobine populations, wild (Ramnagar) and provisioned (Jodhpur) Hanuman langurs, wild Phayre's leaf monkeys (Phu Khieo Wildlife Sanctuary), and captive silvered langurs (Wildlife Conservation Society's Bronx Zoo) were analyzed with respect to reproductive and behavioral trends of aging. All but one female (from a total of seven) became menopausal 1.8 to 5+ years prior to death with a lag time between last parturition and death ranging from 3.0 to 9.0 years (n=8). Hormonal analysis revealed constantly low and acyclic levels of immunoreactive pregnanediol-3-glucuronide (iPdG) in one old, wild female supporting the notion of true menopause. Nonsexual behavior was analyzed based on quantitative data collected for 6 old and 26 younger, adult females simultaneously (1,378.5 h). No support was found for social disengagement, but old females were more inactive and spent less time feeding. Altogether the data support earlier claims of menopause and extended postreproductive life spans in colobine monkeys. Future behavioral studies should aim at longitudinal assessments of behavioral changes and incorporate energetic data as well as testing of social continuity and selectivity.

Understanding the way prosimian primates age can be helpful in inferring what the 'basal primate mode' of senescence may have been. Even though prosimians are known to be long-lived in captivity, relatively little is known about their reproductive senescence, and even less is known about how prosimians age in their natural habitats. Twenty years of observational data in Madagascar for four Propithecus edwardsi sifaka groups were used to analyze reproductive and behavioral trends of aging in the wild. Techniques using tooth wear were developed to establish ages of wild sifakas and to estimate the onset of their 'dental senescence', a proxy for the onset of decline in the ability to obtain nutrition. Estimated maximum longevity was 32 years for female sifakas. Based on the loss of dental functional morphology, and changes in tooth wear patterns and in chewing efficiency, dental senescence was estimated to set in at approximately 18 years of age. Of the adult females in the study groups, the yearly average of the number of dentally senescent females was 24%. There was no indication of a decline in fertility in the dentally senescent females (aged >18 years) compared to younger adult females (aged 4-18 years). The field data showed, however, that in years when rain was decreased during months of prime lactation, infants of dentally senescent mothers died before weaning. This may be because the nursing mother's worn teeth could not shear leaves and extract moisture, nor nutrition, both essential for successful lactation. Old females showed no clear signs of social disengagement, further suggesting that drought-induced stress plays a direct role in increased infant mortality. These data support earlier findings that prosimian females continue to cycle and give birth until death. The effect of environmental variation on infant survival, however, indicates an incipient age-linked decline in reproductive fitness. Therefore, whereas lemurs represent the condition of no menopause, changes in infant survival may uncover selective factors that have in part led to the evolution of menopause in other primates.

Data from wild populations demonstrate that orangutans have the slowest life history of all the great apes. In this chapter, we provide an overview of reproduction and life history traits of female orangutans in the wild and captivity. This comparison of wild and captive data illustrates the variability that exists for orangutans. Wild orangutan females first reproduce at a mean age of 15.4 years, with an age range of 13-18 years, and they have a mean interbirth interval of 9.3 years. Wild male orangutans are conservatively estimated to live at least 58 years, and 53 years for females [1], and to date, there is no evidence to suggest that wild orangutans experience reproductive senescence. We use captive data from 2,566 individuals to show that in captivity orangutan females regularly begin reproducing at the age of 7 and have interbirth intervals that can be shorter than 1 year. We provide additional data that describe the onset and normalization of menses in a young adolescent orangutan as well as the reproductive cycles of three adult females of different ages. Although captive females routinely cycle and reproduce throughout much of their lifespan, age at last reproduction in captivity is 41, which is well before maximum female lifespan. To date, longevity in the wild and in captivity appears equivalent [2]. The reasons for the presence of a postreproductive lifespan in captivity as opposed to its absence in wild populations may be related to management issues. The above results indicate a need for more detailed comparisons between wild and captive orangutans using similar methodologies.

We here examine interindividual variability in reproductive aging in free-ranging female rhesus macaques (Macaca mulatta). Our study site, Raccoon Key, is an island, about 81 hectares in area, situated in the Gulf of Mexico. Our data were collected from 1992 to 1998; the last 7 years a large population of provisioned macaques were resident on the island. We have previously demonstrated that the birth rate realized by the Raccoon Key rhesus in aggregate declined incrementally with female age beginning in the second half of the first decade of life. In this paper, we examine females aged 4-27 years that reproduce annually (annual producers) or, alternatively, fail to reproduce at all (nonproducers) over a period of 4 years. If all females within a given population experience an incremental loss of reproductive capacity with each year of age, the observed number of nonproducers would increase, and the number of producers would decrease with female age, but not above chance levels. However, within the Raccoon Key rhesus macaque population, both did occur at frequencies greater than expected by chance alone indicating there is strong heterogeneity in female fertility. We argue that a sudden catastrophic loss of fertility by a minority of females each year is most consistent with our data, and argue that this outcome is consistent with the evolutionary theory of aging.