The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process

Sex differential in mortality trends of old-aged Danes: a nation wide study of age, period and cohort effects

Objective Over the last half century the mortality rates in Denmark for females above age 80 have declined dramatically whereas the decline for males have been modest, resulting in a change in sex-ratio for centenarians from 2 to 5. Here we investigate whether this mortality pattern is mainly explained by period effects, cohort effects or both. This can provide clues for where to search for causes behind the changes in sex differential in mortality seen in many Western countries during the last decades. Methods Age-period-cohort study of mortality for all Danish women and men aged 79–98 during the period 1949–2006. Outcome measures Relative risks for deaths and second order differences for exploration of the nonlinear variation. Results Both the overall trends in mortality differences and the fluctuations in mortality for both men and women were better explained by period effects than by cohort effects. The observed rates were better described by the age, period and cohort model than by other models. Conclusions Our results suggest that causes for both the overall increased difference in mortality and the short term fluctuations in mortality rates are primarily to be found in the period dimension. Cohort effects on the mortality of the oldest Danish women and men played a significant but minor role compared to period effects

In Vitro Cellular Adaptations of Indicators of Longevity in Response to Treatment with Serum Collected from Humans on Calorie Restricted Diets

Calorie restriction (CR) produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF) and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL) animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals. Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period). Cells cultured in serum from ADF participants, showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1α mRNA levels. This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity. The use of this in vitro technique may be helpful for predicting the potential of CR, ADF and other dietary manipulations to affect markers of longevity in humans

Helper Response to Experimentally Manipulated Predation Risk in the Cooperatively Breeding Cichlid Neolamprologus pulcher

Background We manipulated predation risk in a field experiment with the cooperatively breeding cichlid Neolamprologus pulcher by releasing no predator, a medium- or a large-sized fish predator inside underwater cages enclosing two to three natural groups. We assessed whether helpers changed their helping behaviour, and whether within-group conflict changed, depending on these treatments, testing three hypotheses: ‘pay-to-stay’ PS, ‘risk avoidance’ RA, or (future) reproductive benefits RB. We also assessed whether helper food intake was reduced under risk, because this might reduce investments in other behaviours to save energy. Methodology/Principal Findings Medium and large helpers fed less under predation risk. Despite this effect helpers invested more in territory defence, but not territory maintenance, under the risk of predation (supporting PS). Experimentally covering only the breeding shelter with sand induced more helper digging under predation risk compared to the control treatment (supporting PS). Aggression towards the introduced predator did not differ between the two predator treatments and increased with group member size and group size (supporting PS and RA). Large helpers increased their help ratio (helping effort/breeder aggression received, ‘punishment’ by the dominant pair in the group) in the predation treatments compared to the control treatment, suggesting they were more willing to PS. Medium helpers did not show such effects. Large helpers also showed a higher submission ratio (submission/ breeder aggression received) in all treatments, compared to the medium helpers (supporting PS). Conclusions/Significance We conclude that predation risk reduces helper food intake, but despite this effect, helpers were more willing to support the breeders, supporting PS. Effects of breeder punishment suggests that PS might be more important for large compared to the medium helpers. Evidence for RA was also detected. Finally, the results were inconsistent with RB

Geographic variation in social organization of Galápagos mockingbirds: ecological correlates of group territoriality and cooperative breeding

To investigate ecological influences on cooperative social organization, I studied the four allopatric species of mockingbirds ( Nesomimus spp.) endemic to the Galápagos archipelago on four islands. On three small, low and arid islands (Genovesa, Champion and Española), mockingbird territories filled all terrestrial habitat, mean group size varied from 4.5 to 14.2 adults, maximum group size ranged from seven to 24 birds, and 70–100% of groups contained more than two birds. San Cristóbal is larger and higher, and it supports a broader range of habitats. At one highland and two coastal sites on this island, mockingbirds did not hold territories in all available habitats, group size averaged 2.2 adults, only 25% of groups were larger than two, and none included more than three adults. Adults dispersed into vacant habitat to establish new territories only on San Cristóbal. Helping behavior has not yet been observed on San Cristóbal, but it occurs on the other three islands. These results support the hypothesis that social groups and cooperative breeding are maintained where limited availability of preferred habitat constrains dispersal. The mechanism relaxing habitat saturation on San Cristóbal, however, remains undetermined. Predation by introduced rats and cats may reduce survival and indirectly reduce group size; these predators are absent from Genovesa, Champion and Española. Differences in food supplies could also affect interand intra-island variation in population density. Variation in social organization among arid coastal sites on the four islands, and similarity between climatically different sites on San Cristóbal, suggest that climatic conditions are less important as determinants of dispersal and breeding. Skews in adult sex ratios also fail to account for inter-island variation in sociality. Although they live in a climatically variable environment, territorial behavior and the physical limits of suitable habitat have an overriding influence on cooperative social organization in Galápagos mockingbirds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46894/1/265_2004_Article_BF00302932.pd