Is That Dog a Pit Bull? A Cross-Country Comparison of Perceptions of Shelter Workers Regarding Breed Identification

Bull breeds are commonly kept as companion animals, but the pit bull terrier is restricted by breed-specific legislation (BSL) in parts of the United States and throughout the United Kingdom. Shelter workers must decide which breed(s) a dog is. This decision may influence the dog's fate, particularly in places with BSL. In this study, shelter workers in the United States and United Kingdom were shown pictures of 20 dogs and were asked what breed each dog was, how they determined each dog's breed, whether each dog was a pit bull, and what they expected the fate of each dog to be. There was much variation in responses both between and within the United States and United Kingdom. UK participants frequently labeled dogs commonly considered by U.S. participants to be pit bulls as Staffordshire bull terriers. UK participants were more likely to say their shelters would euthanize dogs deemed to be pit bulls. Most participants noted using dogs' physical features to determine breed, and 41% affected by BSL indicated they would knowingly mislabel a dog of a restricted breed, presumably to increase the dog's adoption chances.     

Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate

Resveratrol, a natural phytoalexin found in grapes and red wine, increases longevity in the short-lived invertebrates Caenorhabditis elegans and Drosophila and exerts a variety of biological effects in vertebrates, including protection from ischemia and neurotoxicity. Its effects on vertebrate lifespan were not yet known. The relatively long lifespan of mice, which live at least 2.5 years, is a hurdle for life-long pharmacological trials. Here, the authors used the short-lived seasonal fish Nothobranchius furzeri with a maximum recorded lifespan of 13 weeks in captivity. Short lifespan in this species is not the result of spontaneous or targeted genetic mutations, but a natural trait correlated with the necessity to breed in an ephemeral habitat and tied with accelerated development and expression of ageing biomarkers at a cellular level. Resveratrol was added to the food starting in early adulthood and caused a dose-dependent increase of median and maximum lifespan. In addition, resveratrol delays the age-dependent decay of locomotor activity and cognitive performances and reduces the expression of neurofibrillary degeneration in the brain. These results demonstrate that food supplementation with resveratrol prolongs lifespan and retards the expression of age-dependent traits in a short-lived vertebrate.     

Age-related changes in the metabolism and body composition of three dog breeds and their relationship to life expectancy

We measured body composition and resting metabolic rates (RMR) of three dog breeds (Papillons, mean body mass 3.0 kg (n = 35), Labrador retrievers, mean body mass 29.8 kg (n = 35) and Great Danes, mean body mass 62.8 kg (n = 35)) that varied between 0.6 and 14.3 years of age. In Papillons, lean body mass (LBM) increased with age but fat mass (FBM) was constant; in Labradors, both LBM and FBM were constant with age, and in Great Danes, FBM increased with age but LBM was constant. FBM averaged 14.8% and 15.7% of body mass in Papillons and Labradors, respectively. Great Danes were leaner and averaged only 10.5% FBM. Pooling the data for all individuals, the RMR was significantly and positively associated with LBM and FBM and negatively associated with age. Once these factors had been taken into account there was still a significant breed effect on RMR, which was significantly lower in Labradors than in the other two breeds. Using the predictive multiple regression equation for RMR and the temporal trends in body composition, we modelled the expenditure of energy (at rest) over the first 8 years of life, and over the entire lifespan for each breed. Over the first 8 years of life the average expenditure of energy per kg LBM were 0.985, 0.675 and 0.662 GJ for Papillons, Labradors and Great Danes, respectively. This energy expenditure was almost 60% greater for the smallest compared with the largest breed. On average, however, the life expectancy for the smallest breed was a further 6 years (i.e. 14 years in total), whereas for the largest breed it was only another 6 months (i.e. 8.5 years in total). Total lifetime expenditure of energy at rest per kg LBM averaged 1.584, 0.918 and 0.691 GJ for Papillons, Labradors and Great Danes, respectively. In Labradors, total daily energy expenditure, measured by the doubly labelled water method in eight animals, was only 16% greater than the observed RMR. High energy expenditure in dogs appears positively linked to increased life expectancy, contrary to the finding across mammal species and within exotherms, yet resembling observations in other intra-specific studies. These contrasting correlations suggest that metabolism is affecting life expectancy in different ways at these different levels of enquiry.     

Molecular structure in peripheral dog breeds: Portuguese native breeds as a case study

Genetic variability in purebred dogs is known to be highly structured, with differences among breeds accounting for ∼30% of the genetic variation. However, analysis of the genetic structure in non-cosmopolitan breeds and local populations is still limited. Nine Portuguese native dog breeds, and other peripheral dog populations (five) with regional affinities, were characterized using 16 microsatellites and 225 amplified fragment length polymorphism (AFLP) markers, and the pattern of genetic differentiation was investigated. Although the level of breed differentiation detected is below that of other dog breeds, there is in most cases a correlation between breed affiliation and molecular structure. AFLP markers and Bayesian clustering methods allowed an average of 73.1% of individuals to be correctly assigned to source populations, providing robust genotypic assessment of breed affiliation. A geographical genetic structure was also detected, which suggests a limited influence of African dogs on the Iberian breeds. The sampling effect on the estimation of population structure was evaluated and there was a 2.2% decrease in genetic differentiation among breeds when working animals were included. Genetic diversity of stray dogs was also assessed and there is no evidence that they pose a threat to the preservation of the gene pool of native dog breeds.     

Lack of age-associated telomere shortening in long- and short-lived species of sea urchins

The red sea urchin, Strongylocentrotus franciscanus, can live in excess of 100 years while the sea urchin Lytechinus variegatus has an estimated lifespan of only 3-4 years. In an effort to understand the molecular mechanism underlying the difference in their longevity we characterized telomere biology in these species of sea urchins. Telomerase activity was found throughout early stages of development in L. variegatus and is maintained in adult tissues of L. variegatus and S. franciscanus. Terminal restriction fragment analysis indicated a lack of age-associated telomere shortening. These data suggest that long- and short-lived sea urchins do not utilize telomerase repression as a mechanism to suppress neoplastic transformation.     

Litter size at birth in purebred dogs--a retrospective study of 224 breeds

Despite the long history of purebred dogs and the large number of existing breeds, few studies of canine litter size based upon a large number of breeds exist. Previous studies are either old or include only one or a few selected breeds. The aim of this large-scale retrospective study was to estimate the mean litter size in a large population of purebred dogs and to describe some factors that might influence the litter size. A total of 10,810 litters of 224 breeds registered in the Norwegian Kennel Club from 2006 to 2007 were included in the study. The overall mean litter size at birth was 5.4 (± 0.025). A generalized linear mixed model with a random intercept for breed revealed that the litter size was significantly influenced by the size of the breed, the method of mating and the age of the bitch. A significant interaction between breed size and age was detected, in that the expected number of puppies born decreased more for older bitches of large breeds. Mean litter size increased with breed size, from 3.5 (± 0.04) puppies in miniature breeds to 7.1 (± 0.13) puppies in giant breeds. No effect on litter size was found for the season of birth or the parity of the bitch. The large number of breeds and the detail of the registered information on the litters in this study are unique. In conclusion, the size of the breed, the age of the bitch and the method of mating were found to influence litter size in purebred dogs when controlling for breed, with the size of the breed as the strongest determinant.     

The pet dogs ability for learning from a human demonstrator in a detour task is independent from the breed and age

There are many indications and much practical knowledge about the different tasks which various breeds of dogs are selected for. Correspondingly these different breeds are known to possess different physical and mental abilities. We hypothesized that commonly kept breeds will show differences in their problem solving ability in a detour task around a V-shaped fence, and also, that breed differences will affect their learning ability from a human demonstrator, who demonstrates a detour around the fence. Subjects were recruited in Hungarian pet dog schools. We compared the results of the 10 most common breeds in our sample when they were tested in the detour task without human demonstration. There was no significant difference between the latencies of detour, however, there was a trend that German Shepherd dogs were the quickest and Giant Schnauzers were the slowest in this test. For testing the social learning ability of dogs we formed three breed groups (“utility”, “shepherd” and “hunting”). There were no significant differences between these, all the breed groups learned equally well from the human demonstrator. However, we found that dogs belonging to the “shepherd” group looked back more frequently to their owner than the dogs in the “hunting” group. Further, we have found that the age of pet dogs did not affect their social learning ability in the detour task. Our results showed that the pet status of a dog has probably a stronger effect on its cognitive performance and human related behaviour than its age or breed. These results emphasize that socialization and common activities with the dog might overcome the possible breed differences, if we give the dogs common problem solving, or social learning tasks.     

Understanding ageing.

A broad biological approach makes it possible to understand why ageing exists and also why different mammalian species have very different maximum longevities. The adult organism is maintained in a functional state by at least ten major mechanisms, which together comprise a substantial proportion of all biological processes. These maintenance mechanisms eventually fail, because the evolved physiological and anatomical design of higher animals is incompatible with continual survival. The lifespan of each mammalian species depends on the efficiency of maintenance of their cells, tissues and organisms, and there is much evidence that such maintenance is more effective in long-lived species, such as man, than in short-lived small mammals. It is also evident that there is an inverse relationship between reproductive potential and longevity, which would be expected if total metabolic resources are shared between investment in reproduction, and investment in the preservation of the adult body. It is proposed that the eventual failure of maintenance leads to the pathological changes seen in age-associated disease. Although we now have a biological understanding of the ageing process, much future research will be needed to uncover the cellular and molecular changes which give rise to age-associated diseases. The major aim of such research is to devise procedures to delay or prevent the onset of these diseases.     

Effects of Phenotypic Characteristics on the Length of Stay of Dogs at Two No Kill Animal Shelters

Adoption records from 2 no kill shelters in New York State were examined to determine how age, sex, size, breed group, and coat color influenced the length of stay (LOS) of dogs at these shelters. Young puppies had the shortest length of stay; LOS among dogs increased linearly as age increased. Neither coat color nor sex influenced LOS. Considering only size classifications, medium-size dogs had the greatest LOS, and extra small dogs and puppies remained in shelters for the least amount of time. Considering only breed groupings, dogs in the guard group had the greatest LOS and those in the giant group had the shortest LOS. The lack of effect of coat color was not expected, nor was the shorter LOS among “fighting” breeds compared with other breed groups. Coat color and breed may have only local effects on LOS that do not generalize to all shelters, including traditional shelters. Understanding the traits of dogs in a specific shelter and the characteristics of these nonhuman animals desired by adopters are critical to improving the welfare of animals served by that shelter.     

Exploring mechanisms of sex differences in longevity: lifetime ovary exposure and exceptional longevity in dogs

To move closer to understanding the mechanistic underpinnings of sex differences in human longevity, we studied pet dogs to determine whether lifetime duration of ovary exposure was associated with exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, age at death, and cause of death for a cohort of canine ‘centenarians’– exceptionally long‐lived Rottweiler dogs that lived more than 30% longer than average life expectancy for the breed. Sex and lifetime ovary exposure in the oldest‐old Rottweilers (age at death, ≥ 13 years) were compared to a cohort of Rottweilers that had usual longevity (age at death, 8.0–10.8 years). Like women, female dogs were more likely than males to achieve exceptional longevity (OR, 95% CI = 2.0, 1.2–3.3; P = 0.006). However, removal of ovaries during the first 4 years of life erased the female survival advantage. In females, a strong positive association between ovaries and longevity persisted in multivariate analysis that considered other factors, such as height, body weight, and mother with exceptional longevity. A beneficial effect of ovaries on longevity in females could not be attributed to resistance against a particular disease or major cause of death. Our results document in dogs a female sex advantage for achieving exceptional longevity and show that lifetime ovary exposure, a factor not previously evaluated in women, is associated with exceptional longevity. This work introduces a conceptual framework for designing additional studies in pet dogs to define the ovary‐sensitive biological processes that promote healthy human longevity.     

Comparison of the longevity and lifetime performance of Scottish Blackface ewes and their crosses within hill sheep flocks

A study was undertaken to compare the longevity and lifetime lamb output of purebred Scottish Blackface (BF) ewes with a range of crossbred genotypes from Scottish BF dams. For up to five successive breeding seasons, 1143 Scottish BF, Swaledale × BF (SW × BF), North Country Cheviot × BF (CH × BF), Lleyn × BF (LL × BF) and Texel × BF (T × BF) ewes were mated to a range of sire breeds on six hill farms across Northern Ireland. Dentition and lamb output were recorded annually until completion of the study or until the ewe was removed due to death or culling. Timing of mortality and the main reason for culling were also recorded. When survival analysis was undertaken, SW × BF and CH × BF ewes had better longevity (P < 0.05) than BF ewes due to their lower culling rate (P < 0.01) and lower mortality rate (P = 0.06), respectively. The relative proportion of LL × BF and T × BF culled due to infertility was lower (P < 0.05) than SW × BF and CH × BF, while a higher (P < 0.05) proportion of LL × BF and T × BF ewes were culled for prolapses compared with the other breed crosses. SW × BF ewes had consistently higher bite scores (P < 0.001) compared with BF, LL × BF and T × BF, indicating a greater prevalence and degree of overshoot. In ewes aged 5.5 years old, SW × BF also had a higher incidence of tooth loss (P < 0.01) compared with the other breeds. However, the proportion of SW × BF culled due to poor teeth condition was lower (P < 0.05) than BF. Across all breeds, the chances of surviving to their next mating were influenced by ewe breed (P < 0.05), age at mating (P < 0.001), body condition score at weaning (P < 0.001), number of missing teeth (P < 0.001) and average daily live weight gain per litter (P < 0.05). The cumulative number and weight of lambs weaned per ewe over five successive matings was higher (P < 0.05) for crossbred compared with pure BF ewes; however there were no differences in lifetime output between the different crossbred ewes studied. This study demonstrates that the higher lamb output of crossbred hill ewes does not compromise their longevity compared with pure Blackface, resulting in greater total lifetime production. When the crossbred ewes are sired by a second hill breed, longevity may be improved.     

Igf-I and longevity

Recent animal studies have demonstrated evidence of the involvement of insulin and insulin-like growth factor (IGF)-I signalling in the control of ageing and longevity. Disruption of insulin/IGF-I signalling pathways significantly extends lifespan in several animal models. Similarities among these signalling pathways in animals and humans raise the possibility that modifications in the IGF-I signalling system could also extend lifespan in humans. However, in contrast to the findings in animal studies, reduced IGF-I activity in humans is not associated with longevity. In humans, low IGF-I activity is even associated with an increased risk of developing cardiovascular disease and diabetes. High IGF-I activity in humans is associated with an increased risk of developing cancer. In addition, genetic predisposition and lifestyle play a major role in determining age-associated disease. For each individual there is probably a specific optimal 'setpoint' for the insulin/growth hormone/IGF-I axis which co-determines survival.     

Reevaluation of T cell receptor excision circles as a measure of human recent thymic emigrants

The human thymus exports newly generated T cells to the periphery. As no markers have been identified for these recent thymic emigrants (RTE), it is presently impossible to measure human thymic output. T cell receptor excision circles (TREC) have been recently used to assess thymic output during both health and disease. Using a mathematical model, we quantify age-dependent changes both in the number of RTE generated per day and in TREC concentration during an 80-year lifespan. Through analyses, we demonstrate that RTE and peripheral T cell division have the same potential to affect TREC concentration at any age in healthy people. T cell death also influences TREC concentration, but to a lesser extent. During aging, our results indicate that thymic involution primarily induces an age-dependent decline in TREC concentrations within both CD4(+) and CD8(+) T cell populations. We further apply this model for studying TREC concentration during HIV-1 infection. Our analyses reveal that a decrease in thymic output is the major contributor to the decline in TREC concentration within CD4(+) T cells, whereas both increased peripheral T cell division and decreased thymic output induce the decline in TREC concentration within CD8(+) T cells. Therefore, we suggest that T cell turnover should be examined together with TREC concentration as a measure of RTE. If peripheral T cell division remains relatively unchanged, then TREC concentration indeed reflects thymic output.     

A one base pair deletion in the canine ATP13A2 gene causes exon skipping and late-onset neuronal ceroid lipofuscinosis in the Tibetan terrier

Neuronal ceroid lipofuscinosis (NCL) is a progressive neurodegenerative disease characterized by brain and retinal atrophy and the intracellular accumulation of autofluorescent lysosomal storage bodies resembling lipofuscin in neurons and other cells. Tibetan terriers show a late-onset lethal form of NCL manifesting first visible signs at 5-7 years of age. Genome-wide association analyses for 12 Tibetan-terrier-NCL-cases and 7 Tibetan-terrier controls using the 127K canine Affymetrix SNP chip and mixed model analysis mapped NCL to dog chromosome (CFA) 2 at 83.71-84.72 Mb. Multipoint linkage and association analyses in 376 Tibetan terriers confirmed this genomic region on CFA2. A mutation analysis for 14 positional candidate genes in two NCL-cases and one control revealed a strongly associated single nucleotide polymorphism (SNP) in the MAPK PM20/PM21 gene and a perfectly with NCL associated single base pair deletion (c.1620delG) within exon 16 of the ATP13A2 gene. The c.1620delG mutation in ATP13A2 causes skipping of exon 16 presumably due to a broken exonic splicing enhancer motif. As a result of this mutation, ATP13A2 lacks 69 amino acids. All known 24 NCL cases were homozygous for this deletion and all obligate 35 NCL-carriers were heterozygous. In a sample of 144 dogs from eleven other breeds, the c.1620delG mutation could not be found. Knowledge of the causative mutation for late-onset NCL in Tibetan terrier allows genetic testing of these dogs to avoid matings of carrier animals. ATP13A2 mutations have been described in familial Parkinson syndrome (PARK9). Tibetan terriers with these mutations provide a valuable model for a PARK9-linked disease and possibly for manganese toxicity in synucleinopathies.     

A breed-matched case-control study of potential risk-factors for canine pyometra

The objective was to evaluate plausible risk-factors for pyometra, a common disease affecting almost 25% of all (unspayed) female dogs before 10 years of age. Because of the strong breed-predilection, an age- and breed-matched case-control study was undertaken on 87 pairs (pyometra-cases and healthy controls) from five breeds (Rottweiler (n = 13), Collie (n = 8), Golden retriever (n = 24), Labrador retriever (n = 16) and German shepherd dog (n = 26)). The mean age was 7.9 y (range 0.8-13.8 y). Variables analyzed included pseudopregnancy, age at first oestrus, length of and regularity of the interoestrus interval, hormone treatments, nulliparity, number of parities, age at first whelping, previous urinary tract infections and mammary tumours. Data were modelled multivariably using matched-pair conditional logistic regression. Analysing interactions with breed, previous pregnancy was statistically associated with pyometra. When amalgamated, in three breeds previous pregnancy was protective (Rottweiler, Collie, Labrador retriever) and in one breed statistically intermediate (German shepherd dog) when compared to the baseline (Golden retriever). Previous pregnancy was a statistically significant factor that had a protective effect against pyometra in some breeds but not in the Golden retriever breed. These findings indicate that protective- and risk-factors may vary between different breeds. The obvious problem with low power and limited possibility for extrapolation, using few dogs in few breeds, is acknowledged. However, it is suggested that failure to control for the confounding effect of breed, especially in epidemiological studies on dog diseases, may lead to potentially erroneous conclusions.     

Sir2 deletion prevents lifespan extension in 32 long-lived mutants

Activation of Sir2 orthologs is proposed to increase lifespan downstream of dietary restriction. Here, we describe an examination of the effect of 32 different lifespan-extending mutations and four methods of DR on replicative lifespan (RLS) in the short-lived sir2Δ yeast strain. In every case, deletion of SIR2 prevented RLS extension; however, RLS extension was restored when both SIR2 and FOB1 were deleted in several cases, demonstrating that SIR2 is not directly required for RLS extension. These findings indicate that suppression of the sir2Δ lifespan defect is a rare phenotype among longevity interventions and suggest that sir2Δ cells senesce rapidly by a mechanism distinct from that of wild-type cells. They also demonstrate that failure to observe lifespan extension in a short-lived background, such as cells or animals lacking sirtuins, should be interpreted with caution.     

Incidence of pyometra in Swedish insured cats

Pyometra is a clinically relevant problem in intact female cats and dogs. The etiology is similar in both animal species, with the disease caused by bacterial infection of a progesterone-sensitized uterus. Here, we studied pyometra in cats with the aim to describe the incidence and probability of developing pyometra based on age and breed. The data used were reimbursed claims for veterinary care insurance or life insurance claims or both in cats insured in a Swedish insurance database from 1999 to 2006. The mean incidence rate (IR) for pyometra was about 17 cats per 10,000 cat years at risk (CYAR). Cats with pyometra were diagnosed at a median age of 4 years and a significant breed effect was observed. The breed with the highest IR (433 cats per 10,000 CYAR) was the Sphynx, and other breeds with IR over 60 cats per 10,000 CYAR were Siberian cat, Ocicat, Korat, Siamese, Ragdoll, Maine coon, and Bengal. Pyometra was more commonly diagnosed with increasing age, with a marked increase in cats older than 7 years. The mean case fatality rate in all cats was 5.7%, which is slightly higher than corresponding reports in dogs of 3% to 4%. Geographical location (urban or rural) did not affect the risk of developing the disease. The present study provides information of incidence and probability of developing pyometra based on age, breed, and urban or rural geographical location. These data may be useful for designing cat breeding programs in high-risk breeds and for future studies of the genetic background of the disease.     

Mitochondrial quality control during inheritance is associated with lifespan and mother-daughter age asymmetry in budding yeast

Fluorescence loss in photobleaching experiments and analysis of mitochondrial function using superoxide and redox potential biosensors revealed that mitochondria within individual yeast cells are physically and functionally distinct. Mitochondria that are retained in mother cells during yeast cell division have a significantly more oxidizing redox potential and higher superoxide levels compared to mitochondria in buds. Retention of mitochondria with more oxidizing redox potential in mother cells occurs to the same extent in young and older cells and can account for the age-associated decline in total cellular mitochondrial redox potential in yeast as they age from 0 to 5 generations. Deletion of Mmr1p, a member of the DSL1 family of tethering proteins that localizes to mitochondria at the bud tip and is required for normal mitochondrial inheritance, produces defects in mitochondrial quality control and heterogeneity in replicative lifespan (RLS). Long-lived mmr1Δ cells exhibit prolonged RLS, reduced mean generation times, more reducing mitochondrial redox potential and lower mitochondrial superoxide levels compared to wild-type cells. Short-lived mmr1Δ cells exhibit the opposite phenotypes. Moreover, short-lived cells give rise exclusively to short-lived cells, while the majority of daughters of long-lived cells are long lived. These findings support the model that the mitochondrial inheritance machinery promotes retention of lower-functioning mitochondria in mother cells and that this process contributes to both mother-daughter age asymmetry and age-associated declines in cellular fitness.     

Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice

A key tenet of the oxidative stress theory of aging is that levels of accrued oxidative damage increase with age. Differences in damage generation and accumulation therefore may underlie the natural variation in species longevity. We compared age-related profiles of whole-organism lipid peroxidation (urinary isoprostanes) and liver lipid damage (malondialdehyde) in long living naked mole-rats [maximum lifespan (MLS) > 28.3 years] and shorter-living CB6F1 hybrid mice (MLS approximately 3.5 years). In addition, we compared age-associated changes in liver non-heme iron to assess how intracellular conditions, which may modulate oxidative processes, are affected by aging. Surprisingly, even at a young age, concentrations of both markers of lipid peroxidation, as well as of iron, were at least twofold (P < 0.005) greater in naked mole tats than in mice. This refutes the hypothesis that prolonged naked mole-rat longevity is due to superior protection against oxidative stress. The age-related profiles of all three parameters were distinctly species specific. Rates of lipid damage generation in mice were maintained throughout adulthood, while accrued damage in old animals was twice that of young mice. In naked mole-rats, urinary isoprostane excretion declined by half with age (P < 0.001), despite increases in tissue iron (P < 0.05). Contrary to the predictions of the oxidative stress theory, lipid damage levels did not change with age in mole-rats. These data suggest that the patterns of age-related changes in levels of markers of oxidative stress are species specific, and that the pronounced longevity of naked mole-rats is independent of oxidative stress parameters.     

Programmed ageing: decline of stem cell renewal,immunosenescence, and Alzheimer's disease

The characteristic maximum lifespan varies enormously across animal species from a few hours to hundreds of years. This argues that maximum lifespan, and the ageing process that itself dictates lifespan, are to a large extent genetically determined. Although controversial, this is supported by firm evidence that semelparous species display evolutionarily programmed ageing in response to reproductive and environmental cues. Parabiosis experiments reveal that ageing is orchestrated systemically through the circulation, accompanied by programmed changes in hormone levels across a lifetime. This implies that, like the circadian and circannual clocks, there is a master ‘clock of age’ (circavital clock) located in the limbic brain of mammals that modulates systemic changes in growth factor and hormone secretion over the lifespan, as well as systemic alterations in gene expression as revealed by genomic methylation analysis. Studies on accelerated ageing in mice, as well as human longevity genes, converge on evolutionarily conserved fibroblast growth factors (FGFs) and their receptors, including KLOTHO, as well as insulin-like growth factors (IGFs) and steroid hormones, as key players mediating the systemic effects of ageing. Age-related changes in these and multiple other factors are inferred to cause a progressive decline in tissue maintenance through failure of stem cell replenishment. This most severely affects the immune system, which requires constant renewal from bone marrow stem cells. Age-related immune decline increases risk of infection whereas lifespan can be extended in germfree animals. This and other evidence suggests that infection is the major cause of death in higher organisms. Immune decline is also associated with age-related diseases. Taking the example of Alzheimer's disease (AD), we assess the evidence that AD is caused by immunosenescence and infection. The signature protein of AD brain, Aβ, is now known to be an antimicrobial peptide, and Aβ deposits in AD brain may be a response to infection rather than a cause of disease. Because some cognitively normal elderly individuals show extensive neuropathology, we argue that the location of the pathology is crucial – specifically, lesions to limbic brain are likely to accentuate immunosenescence, and could thus underlie a vicious cycle of accelerated immune decline and microbial proliferation that culminates in AD. This general model may extend to other age-related diseases, and we propose a general paradigm of organismal senescence in which declining stem cell proliferation leads to programmed immunosenescence and mortality.