Long-lived Mammals Research Articles

Sowing the seeds of cancer

Advances in the health system and medical sciences are continuously pushing the barrier of life-expectancy. As a consequence, humans are being increasingly afflicted by age-associated diseases, such as cancer. The challenge now lies in understanding the mechanisms underlying ageing in order to reduce the lifetime risk for cancer. In long-lived mammals, telomere length and restriction of telomerase activity are important barriers preventing the uncontrolled cell division. Absence of telomerase dictates the continuous telomere erosion with each cell division, thus restraining the proliferation of incipient tumour cells. However, recent findings have revealed the unintended consequences of telomere control of cell division. Cells with short telomeres accumulate in older individuals increasing the risk of telomere depletion. Loss of telomere protection results in tetraploidization and genomic instability characteristic of epithelial cancers. Additionally, telomere shortening blocks cell proliferation and induces cell senescence. Senescent cells secrete proinflammatory factors and reactive oxygen species that increase the likelihood of cellular transformation and create the perfect soil for cancer development. Telomere shortening thus provides an example of antagonist pleiotropy, in which a beneficial characteristic that acts during the reproductive years of an organism may, later in life, contain the seed to its demise.

Mark-Recapture Analysis of the Critically Endangered Eastern Taiwan Strait Population of Indo-Pacific Humpback Dolphins (Sousa Chinensis): Implications for Conservation

Accurate and precise estimates of abundance and survival rates are important for assessing the conservation status of cetacean populations. Mark-recapture analysis of photo-identification data of the critically endangered eastern Taiwan Strait (ETS) population of Indo-Pacific humpback dolphin, Sousa chinensis (Osbeck, 1765), was conducted on data collected between 2007 and 2010 to refine a preliminary, and the only available, abundance estimate for this isolated population (n = 99; CV = 51.6%), as well as to provide survival rates. About 14,000 good quality photographs (about 2100-6300 yr-1) were used to estimate both parameters for marked animals under Pollock's Robust Design model. The total population size (NT) was determined by correcting for the proportion of the population possessing long-lasting marks (?). The annual point estimates were lower, varying from 54 to 74, and had much better precision (CV varied from 4% to 13%) than previous estimates, suggesting that mark-recapture is a suitable method for estimating abundance of this population. These estimates also further supported the precarious state of the ETS population under another criterion of the IUCN Red List of Threatened Species. As expected for long-lived mammals, annual apparent survival rate was high at 0.985 (95% CI = 0.832-0.998). Continuing to monitor the ETS population of humpback dolphins with such high precision and accuracy will allow examination of the population's trends over time and to better understand its future persistence.

Activity re-assignment and microclimate selection of free-living Arabian oryx: responses that could minimise the effects of climate change on homeostasis?

Predicting whether behaviour could buffer the effects of climate change on long-lived mammals requires a better understanding of the long-term behavioural responses of mammals to environmental stress. Using biologging, we measured locomotor activity and microclimate selection, over eight months, in five Arabian oryx (Oryx leucoryx) living free in a Saudi Arabian desert. The oryx displayed seasonal flexibility in activity patterns, shifting from a continuous 24-h activity pattern with crepuscular peaks in cooler months to a predominantly nocturnal activity pattern during the hottest months, without reducing the total 24-h activity level. The proportion of total 24-h activity that occurred during daylight hours was just 29±8% during the hottest months, versus 53±8% (mean±SD, n=5 oryx) in the other months. The attenuation in diurnal activity levels during the hot months was accompanied by the selection of cooler microclimates, presumably via shade seeking, during the heat of the day. Analysis of miniature black globe (miniglobe) temperature from a remote sensor on the collar of two female animals revealed that oryx selected microclimates cooler than the microclimates in direct sun at higher environmental heat loads across all periods, but with enhanced efficiency during the dry periods. We have quantified activity re-assignment and microclimate selection as responses to hot arid conditions in a free-living artiodactyl. Such flexible behavioural processes may act to buffer the adverse effects of the progressively hotter and drier conditions predicted to occur with climate change.

Genomic Evidence for Large, Long-Lived Ancestors to Placental Mammals

It is widely assumed that our mammalian ancestors, which lived in the Cretaceous era, were tiny animals that survived massive asteroid impacts in shelters and evolved into modern forms after dinosaurs went extinct, 65 Ma. The small size of most Mesozoic mammalian fossils essentially supports this view. Paleontology, however, is not conclusive regarding the ancestry of extant mammals, because Cretaceous and Paleocene fossils are not easily linked to modern lineages. Here, we use full-genome data to estimate the longevity and body mass of early placental mammals. Analyzing 36 fully sequenced mammalian genomes, we reconstruct two aspects of the ancestral genome dynamics, namely GC-content evolution and nonsynonymous over synonymous rate ratio. Linking these molecular evolutionary processes to life-history traits in modern species, we estimate that early placental mammals had a life span above 25 years and a body mass above 1 kg. This is similar to current primates, cetartiodactyls, or carnivores, but markedly different from mice or shrews, challenging the dominant view about mammalian origin and evolution. Our results imply that long-lived mammals existed in the Cretaceous era and were the most successful in evolution, opening new perspectives about the conditions for survival to the Cretaceous-Tertiary crisis.

Moss, C. J., H. Croze, and P. C. Lee (eds.).2011. The Amboseli Elephants: A Long-term Perspective on a Long-lived Mammal. University of Chicago Press, Chicago, Illinois, 383 pp. ISBN-13 978-0-226-54223-2 and ISBN-10 0-226-54223-8, price (hardbound), $65.00.

C. J. Moss, H. Croze, P. C. Lee (eds.). 2011. The Amboseli Elephants: A Long-term Perspective on a Long-lived Mammal. University of Chicago Press, Chicago, Illinois, 383 pp. ISBN-13 978-0-226-54223-2 and ISBN-10 0-226-54223-8, price (hardbound), $65.00. A 38-year program of research on a single population, the Amboseli Elephant Research Project, stands as a pinnacle example of mammalogy for its length and depth of investigation. This study, widely known through the scientific and popular writing of Cynthia Moss and Joyce Poole, is now put into full scientific context in this edited multiauthor volume that was 12 years in the making, or as the authors point out, “the gestation period of 5–6 elephant calves.” What the authors have achieved is not just a reference on the Amboseli population, but a compendium of biological, ecological, and natural history knowledge on elephants. By comparison, all the other great books on elephant behavior read more like travelogues or biographies. Be warned, readers looking for the common coffee table book with large glossy color photos and field anecdotes will be sorely disappointed. Appealingly, this book instead focuses on providing a well-organized overview of the Amboseli system and the elephants within it by summarizing previously published research findings (with updated information), as well as novel information not published in the peer-reviewed literature during this long-term project. The book is organized into 5 parts. In Part 1, the editors set the background for their subsequent detailed sections on elephant behavior. Harvey Croze and Keith Lindsay provide a background chapter devoted to the biotic and abiotic conditions of Amboseli and how those conditions changed over time. Kadzo Kangwana and Christine Brown-Nunez provide an intriguing and detailed account of how Maasai communities surrounding the park are shifting toward a more sedentary agricultural lifestyle that is incorporated into the commercial economy. Treated objectively in Part 1, the increasing importance of human land use and interactions with elephants is a recurrent theme throughout the book, and is revisited from the perspective of Amboseli Elephant Research Project proponents in …

Senescence and age‐specific trade‐offs between reproduction and survival in female Asian elephants

Although studies on laboratory species and natural populations of vertebrates have shown reproduction to impair later performance, little is known of the age-specific associations between reproduction and survival, and how such findings apply to the ageing of large, long-lived species. Herein we develop a framework to examine population-level patterns of reproduction and survival across lifespan in long-lived organisms, and decompose those changes into individual-level effects, and the effects of age-specific trade-offs between fitness components. We apply this to an extensive longitudinal dataset on female semi-captive Asian timber elephants (Elephas maximus) and report the first evidence of age-specific fitness declines that are driven by age-specific associations between fitness components in a long-lived mammal. Associations between reproduction and survival are positive in early life, but negative in later life with up to 71% of later-life survival declines associated with investing in the production of offspring within this population of this critically endangered species.

The Amboseli elephants: a long-term perspective on a long-lived mammal

The Amboseli elephants: a long-term perspective on a long-lived mammal

Comparing adult hippocampal neurogenesis in mammalian species and orders: influence of chronological age and life history stage

Adult hippocampal neurogenesis is a prominent event in rodents. In species with longer life expectancies, newly born cells in the adult dentate gyrus of the hippocampal formation are less abundant or can be completely absent. Several lines of evidence indicate that the regulatory mechanisms of adult neurogenesis differ between short- and long-lived mammals. After a critical appraisal of the factors and problems associated with comparing different species, we provide a quantitative comparison derived from seven laboratory strains of mice (BALB, C57BL/6, CD1, outbred) and rats (F344, Sprague-Dawley, Wistar), six other rodent species of which four are wild-derived (wood mouse, vole, spiny mouse and guinea pig), three non-human primate species (marmoset and two macaque species) and one carnivore (red fox). Normalizing the number of proliferating cells to total granule cell number, we observe an overall exponential decline in proliferation that is chronologically equal between species and orders and independent of early developmental processes and life span. Long- and short-lived mammals differ with regard to major life history stages; at the time points of weaning, age at first reproduction and average life expectancy, long-lived primates and foxes have significantly fewer proliferating cells than rodents. Although the database for neuronal differentiation is limited, we find indications that the extent of neuronal differentiation is subject to species-specific selective adaptations. We conclude that absolute age is the critical factor regulating cell genesis in the adult hippocampus of mammals. Ontogenetic and ecological factors primarily influence the regulation of neuronal differentiation rather than the rate of cell proliferation.

Cynthia J. Moss, Harvey Croze, and Phyllis C. Lee (Eds.): The Amboseli Elephants: A Long-Term Perspective on a Long-Lived Mammal

Cynthia J. Moss, Harvey Croze, and Phyllis C. Lee (Eds.): The Amboseli Elephants: A Long-Term Perspective on a Long-Lived Mammal

Health and condition in the adult Weddell seal of McMurdo Sound, Antarctica

Weddell seals ( Leptonychotes weddellii) are large-bodied, long-lived mammals that live only in the circumpolar Antarctic. As such, they represent an ideal sentinel species for the impacts of environmental change on polar species. However, longitudinal physiological studies of marine mammals are notoriously difficult due to their largely aquatic lifestyle, such that many baseline indicators of health and condition are not well defined. Fifty known-age, adult seals (9–27 years, 24 males, 26 females) in McMurdo Sound were sampled for mass, total body fat, blubber depth and a suite of blood parameters (21 variables) to assess hydration state, nutritional plane, reproductive hormones (females only), organ function and immune status. Total body mass increased with age, whereas variation in blubber depth was best described by mass and/or sex, with an overall greater blubber thickness in female seals ( p < 0.001). Ten blood parameters showed a significant effect of one or more model variables, most prominently between the sexes. Serum chemistry suggested that females were better nourished and displayed lower indicators of acute stress compared to males. We noted limited age-related declines that might indicate impaired organ function. Overall, seals demonstrated clinically normal values for large mammals, even at the upper end of the age continuum. Future physiological studies in this species are strongly encouraged to incorporate potential sex effects in experimental design and analysis.

Bats

Bats

Effects of early horn growth on reproduction and hunting mortality in female chamois

1. Environmental conditions during early development can affect the growth patterns of vertebrates, influencing future survival and reproduction. In long-lived mammals, females that experience poor environmental conditions early in life may delay primiparity. In female bovids, annual horn growth increments may provide a record of age-specific reproduction and body growth. Horn length, however, may also be a criterion used by hunters in selecting animals to harvest, possibly leading to artificial selection. 2. We studied three populations of chamois (Rupicapra rupicapra) in the western Alps to explore the relationships between female horn length and early growth, age of primiparity and age-specific reproduction. We also compared the risk of harvest to reproductive status and horn length. 3. Early horn growth was positively correlated with body mass in pre-reproductive females and with reproduction in very young and senescent adults. Females with strong early horn growth attained primiparity at an earlier age than those with weak early growth. Horn length did not affect hunter selection, but we found a strong hunter preference for nonlactating females. 4. Our research highlights the persistent effects of early development on reproductive performance in mammals. Moderate sport harvests are unlikely to affect the evolution of phenotypic traits and reproductive strategies in female chamois. A policy of penalizing hunters that harvest lactating females, however, may increase the harvest of 2-year-old females, which have high reproductive potential.

The β-Blocker Atenolol Lowers the Longevity-Related Degree of Fatty Acid Unsaturation, Decreases Protein Oxidative Damage, and Increases Extracellular Signal-Regulated Kinase Signaling in the Heart of C57BL/6 Mice

The interruption of the β-adrenergic receptor signaling at the level of adenylyl cyclase (AC) by specifically knocking out (KO) the AC5 gene activates the RAF/MEK/ extracellular signal-regulated kinase (ERK) signaling pathway, delays bone and heart aging, and increases mean and maximum longevity in mice. However, the mechanisms involved in life extension in this animal model with increased longevity have not been clarified, although a decrease in oxidative stress has been proposed as mediator. Two traits link longevity and oxidative stress. Long-lived mammals and birds have a low rate of mitochondrial reactive oxygen species (mitROS) generation and a low degree of membrane fatty acid unsaturation, but these key factors have not been studied in AC5 KO mice. In the present investigation, male C57BL/6 mice were treated with the β-blocker atenolol in drinking water, and oxidative stress-related parameters were measured in the heart. Atenolol treatment did not change the rate of mitROS production and oxidative damage to mitDNA (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]), but strongly decreased the degree of fatty acid unsaturation and the peroxidizability index, mainly due to decreases in 22:6n-3 and 20:4n-6 and to increases in 18:1n-9, 16:1n-7 and 16:0 in the atenolol group. Protein oxidation and lipoxidation were lower in the atenolol group than in the controls. The mitochondrial complex I and IV content and the amount of p-ERK1/2 signaling proteins were significantly higher in the atenolol-treated than in the control animals. These results support the idea that the increased longevity of the AC5 KO mice can be due in part to an ERK signaling-mediated stress-resistance due to a decrease in fatty acid unsaturation, leading to lower lipid peroxidation and decreased lipoxidation-derived damage to cellular proteins.

Senescence Is More Important in the Natural Lives of Long- Than Short-Lived Mammals

BackgroundSenescence has been widely detected among mammals, but its importance to fitness in wild populations remains controversial. According to evolutionary theories, senescence occurs at an age when selection is relatively weak, which in mammals can be predicted by adult survival rates. However, a recent analysis of senescence rates found more age-dependent mortalities in natural populations of longer lived mammal species. This has important implications to ageing research and for understanding the ecological relevance of senescence, yet so far these have not been widely appreciated. We re-address this question by comparing the mean and maximum life span of 125 mammal species. Specifically, we test the hypothesis that senescence occurs at a younger age relative to the mean natural life span in longer lived species.Methodology/Principal FindingsWe show, using phylogenetically-informed generalised least squares models, a significant log-log relationship between mean life span, as calculated from estimates of adult survival for natural populations, and maximum recorded life span among mammals (R2 = 0.57, p<0.0001). This provides further support for a key prediction of evolutionary theories of ageing. The slope of this relationship (0.353±0.052 s.e.m.), however, indicated that mammals with higher survival rates have a mean life span representing a greater fraction of their potential maximum life span: the ratio of maximum to mean life span decreased significantly from >10 in short-lived to ∼1.5 in long-lived mammal species.Conclusions/SignificanceWe interpret the ratio of maximum to mean life span to be an index of the likelihood an individual will experience senescence, which largely determines maximum life span. Our results suggest that senescence occurs at an earlier age relative to the mean life span, and therefore is experienced by more individuals and remains under selection pressure, in long- compared to short-lived mammals. A minimum rate of somatic degradation may ultimately limit the natural life span of mammals. Our results also indicate that senescence and modulating factors like oxidative stress are increasingly important to the fitness of longer lived mammals (and vice versa).

Resistance to experimental tumorigenesis in cells of a long‐lived mammal, the naked mole‐rat (Heterocephalus glaber)

The naked mole-rat (NMR, Heterocephalus glaber) is a long-lived mammal in which spontaneous cancer has not been observed. To investigate possible mechanisms for cancer resistance in this species, we studied the properties of skin fibroblasts from the NMR following transduction with oncogenes that cause cells of other mammalian species to form malignant tumors. Naked mole-rat fibroblasts were transduced with a retrovirus encoding SV40 large T antigen and oncogenic Ras(G12V). Following transplantation of transduced cells into immunodeficient mice, cells rapidly entered crisis, as evidenced by the presence of anaphase bridges, giant cells with enlarged nuclei, multinucleated cells, and cells with large number of chromosomes or abnormal chromatin material. In contrast, similarly transduced mouse and rat fibroblasts formed tumors that grew rapidly without crisis. Crisis was also observed after > 40 population doublings in SV40 TAg/Ras-expressing NMR cells in culture. Crisis in culture was prevented by additional infection of the cells with a retrovirus encoding hTERT (telomerase reverse transcriptase). SV40 TAg/Ras/hTERT-expressing NMR cells formed tumors that grew rapidly in immunodeficient mice without evidence of crisis. Crisis could also be induced in SV40 TAg/Ras-expressing NMR cells by loss of anchorage, but after hTERT transduction, cells were able to proliferate normally following loss of anchorage. Thus, rapid crisis is a response of oncogene-expressing NMR cells to growth in an in vivo environment, which requires anchorage independence, and hTERT permits cells to avoid crisis and to achieve malignant tumor growth. The unique reaction of NMR cells to oncogene expression may form part of the cancer resistance of this species.

Strong and Consistent Social Bonds Enhance the Longevity of Female Baboons

Longevity is a major component of variation in fitness in long-lived iteroparous species [1-4]. Among female baboons, variation in breeding lifespan accounts for approximately 50% of the variation in lifetime fitness [5, 6]. However, we know little about the causes of variation in longevity in primates or other long-lived mammals. Savannah baboons form strong, equitable, and enduring relationships with specific female partners, particularly with close relatives and agemates [7-10]. The quality of females' social relationships influences their ability to cope with stressful events [11-13] and is associated with variation in female reproductive success [9, 14]. Here we show that dominance rank and the quality of close social bonds have independent effects on the longevity of female chacma baboons (Papio hamadryas ursinus). High-ranking females live longer than lower-ranking females. In addition, females who form stronger and more stable social bonds with other females live significantly longer than females who form weaker and less stable relationships. These data extend our understanding of the adaptive value of social bonds in baboons and complement a growing body of evidence that indicates that social bonds have adaptive value in a range of taxa, from mice to humans [9, 14-19].

Age- and sex-specific survival estimates incorporating tag loss for New Zealand sea lions,Phocarctos hookeri

The estimation of life-history parameters for a threatened species is important for understanding its biology and helping to determine management options. This research investigates age- and sex-related survival estimates incorporating tag loss for New Zealand (NZ) sea lions (Phocarctos hookeri) from Sandy Bay, Enderby Island, Auckland Islands, New Zealand, using multistate mark-recapture data from known-age individuals over 8 years (1997–1998 to 2005–2006). Survival estimates and tag loss rates differed significantly by sex and age class, with adult males having the lowest tag retention of any age or sex class and females ≥ 3 years old having lower survival estimates than their male counterparts. The variability and lower female survival relative to males is a critical problem for NZ sea lions, because even small changes in adult female survival significantly affect population trends for such large, long-lived mammals.

Observational evidence of risk-sensitive reproductive allocation in a long-lived mammal

Organisms should adopt a risk-sensitive reproductive allocation when summer reproductive allocation competes with survival in the coming winter. This trade off is shown through autumn female body mass, which acts as an insurance against unpredictable winter environmental conditions. We tested this hypothesis on female reindeer in a population that has experienced a time period of dramatic increase in abundance. Environmental conditions during winter were fairly stable (with the exception of 1 year). We conclude that increased population abundance (perhaps in interaction with winter environmental conditions) could have represented a worsening of winter environmental conditions as both autumn offspring and spring female body mass decreased during the course of the study. Moreover, we found that the cost of reproduction was related to environmental conditions as: (1) autumn body mass was larger for barren than for lactating females, and this difference was temporally highly variable; (2) lactating females produced smaller offspring than barren ones in the following year; and (3) reproductive output (offspring size) decreased over time. We also found evidence of quality effects as lactating females had a higher reproductive success in the following year. In sum, a worsening of winter conditions lead to: (1) decreased reproductive output; (2) lowered autumn body mass for lactating females; and (3) increased body mass for barren females. Since females reduce their reproductive allocation as winter conditions becomes more severe, we conclude that reindeer have adopted a risk-sensitive reproductive allocation.

Climate change and seasonal reproduction in mammals

Seasonal reproduction is common among mammals at all latitudes, even in the deep tropics. This paper (i) discusses the neuroendocrine pathways via which foraging conditions and predictive cues such as photoperiod enforce seasonality, (ii) considers the kinds of seasonal challenges mammals actually face in natural habitats, and (iii) uses the information thus generated to suggest how seasonal reproduction might be influenced by global climate change. Food availability and ambient temperature determine energy balance, and variation in energy balance is the ultimate cause of seasonal breeding in all mammals and the proximate cause in many. Photoperiodic cueing is common among long-lived mammals from the highest latitudes down to the mid-tropics. It is much less common in shorter lived mammals at all latitudes. An unknown predictive cue triggers reproduction in some desert and dry grassland species when it rains. The available information suggests that as our climate changes the small rodents of the world may adapt rather easily but the longer lived mammals whose reproduction is regulated by photoperiod may not do so well. A major gap in our knowledge concerns the tropics; that is where most species live and where we have the least understanding of how reproduction is regulated by environmental factors.

Telomeres and disease

The telomeres of most eukaryotes are characterized by guanine-rich repeats synthesized by the reverse transcriptase telomerase. Complete loss of telomerase is tolerated for several generations in most species, but modestly reduced telomerase levels in human beings are implicated in bone marrow failure, pulmonary fibrosis and a spectrum of other diseases including cancer. Differences in telomerase deficiency phenotypes between species most likely reflect a tumour suppressor function of telomeres in long-lived mammals that does not exist as such in short-lived organisms. Another puzzle provided by current observations is that family members with the same genetic defect, haplo-insufficiency for one of the telomerase genes, can present with widely different diseases. Here, the crucial role of telomeres and telomerase in human (stem cell) biology is discussed from a Darwinian perspective. It is proposed that the variable phenotype and penetrance of heritable human telomerase deficiencies result from additional environmental, genetic and stochastic factors or combinations thereof.