The new biology of ageing

Human life expectancy in developed countries has increased steadily for over 150 years, through improvements in public health and lifestyle. More people are hence living long enough to suffer age-related loss of function and disease, and there is a need to improve the health of older people. Ageing is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. This view has been reinforced by the realization that ageing is a disadvantageous trait that evolves as a side effect of mutation accumulation or a benefit to the young, because of the decline in the force of natural selection at later ages. However, important recent discoveries are that mutations in single genes can extend lifespan of laboratory model organisms and that the mechanisms involved are conserved across large evolutionary distances, including to mammals. These mutations keep the animals functional and pathology-free to later ages, and they can protect against specific ageing-related diseases, including neurodegenerative disease and cancer. Preliminary indications suggest that these new findings from the laboratory may well also apply to humans. Translating these discoveries into medical treatments poses new challenges, including changing clinical thinking towards broad-spectrum, preventative medicine and finding novel routes to drug development

Individual variation in age‐dependent reproduction: Fast explorers live fast but senesce young?

Adaptive integration of life history and behaviour is expected to result in variation in the pace‐of‐life. Previous work focused on whether ‘risky’ phenotypes live fast but die young, but reported conflicting support. We posit that individuals exhibiting risky phenotypes may alternatively invest heavily in early‐life reproduction but consequently suffer greater reproductive senescence. We used a 7‐year longitudinal dataset with >1,200 breeding records of >800 female great tits assayed annually for exploratory behaviour to test whether within‐individual age dependency of reproduction varied with exploratory behaviour. We controlled for biasing effects of selective (dis)appearance and within‐individual behavioural plasticity. Slower and faster explorers produced moderate‐sized clutches when young; faster explorers subsequently showed an increase in clutch size that diminished with age (with moderate support for declines when old), whereas slower explorers produced moderate‐sized clutches throughout their lives. There was some evidence that the same pattern characterized annual fledgling success, if so, unpredictable environmental effects diluted personality‐related differences in this downstream reproductive trait. Support for age‐related selective appearance was apparent, but only when failing to appreciate within‐individual plasticity in reproduction and behaviour. Our study identifies within‐individual age‐dependent reproduction, and reproductive senescence, as key components of life‐history strategies that vary between individuals differing in risky behaviour. Future research should thus incorporate age‐dependent reproduction in pace‐of‐life studies

Dietary and serum tyrosine, white matter microstructure and inter-individual variability in executive functions in overweight adults: Relation to sex/gender and age

Tyrosine (tyr), the precursor of the neurotransmitter dopamine, is known to modulate cognitive functions including executive attention. Tyr supplementation is suggested to influence dopamine-modulated cognitive performance. However, results are inconclusive regarding the presence or strength and also the direction of the association between tyr and cognitive function. This pre-registered cross-sectional analysis investigates whether diet-associated serum tyr relates to executive attention performance, and whether this relationship is moderated by differences in white matter microstructure. 59 healthy, overweight, young to middle-aged adults (20 female, 28.3 ± 6.6 years, BMI: 27.3 ± 1.5 kg/m2) drawn from a longitudinal study reported dietary habits, donated blood and completed diffusion-weighted brain magnetic resonance imaging and the attention network test. Main analyses were performed using linear regressions and non-parametric voxel-wise inference testing. Confirmatory analyses did neither support an association between dietary and serum tyr nor a relationship between relative serum tyr/large neutral amino acids (LNAA) levels or white matter microstructure and executive attention performance. However, exploratory analyses revealed higher tyr intake, higher serum tyr and better executive attention performance in the male sex/gender group. In addition, older age was associated with higher dietary tyr intake and lower fractional anisotropy in a widespread cluster across the brain. Finally, a positive association between relative serum tyr/LNAA and executive attention performance was found in the male sex/gender group when accounting for age effects. Our analysis advances the field of dopamine-modulated cognitive functions by revealing sex/gender and age differences which might be diet-related. Longitudinal or intervention studies and larger sample sizes are needed to provide more reliable evidence for links between tyr and executive attention

Analytical solution of a generalized Penna model

In 1995 T.J.Penna introduced a simple model of biological aging. A modified Penna model has been demonstrated to exhibit behaviour of real-life systems including catastrophic senescence in salmon and a mortality plateau at advanced ages. We present a general steady-state, analytic solution to the Penna model, able to deal with arbitrary birth and survivability functions. This solution is employed to solve standard variant Penna models studied by simulation. Different Verhulst factors regulating both the birth rate and external death rate are considered.Comment: 6 figure

Time evolution of the Partridge-Barton Model

The time evolution of the Partridge-Barton model in the presence of the pleiotropic constraint and deleterious somatic mutations is exactly solved for arbitrary fecundity in the context of a matricial formalism. Analytical expressions for the time dependence of the mean survival probabilities are derived. Using the fact that the asymptotic behavior for large time $t$ is controlled by the largest matrix eigenvalue, we obtain the steady state values for the mean survival probabilities and the Malthusian growth exponent. The mean age of the population exhibits a $t^{-1}$ power law decayment. Some Monte Carlo simulations were also performed and they corroborated our theoretical results.Comment: 10 pages, Latex, 1 postscript figure, published in Phys. Rev. E 61, 5664 (2000

Change and Aging Senescence as an adaptation

Understanding why we age is a long-lived open problem in evolutionary biology. Aging is prejudicial to the individual and evolutionary forces should prevent it, but many species show signs of senescence as individuals age. Here, I will propose a model for aging based on assumptions that are compatible with evolutionary theory: i) competition is between individuals; ii) there is some degree of locality, so quite often competition will between parents and their progeny; iii) optimal conditions are not stationary, mutation helps each species to keep competitive. When conditions change, a senescent species can drive immortal competitors to extinction. This counter-intuitive result arises from the pruning caused by the death of elder individuals. When there is change and mutation, each generation is slightly better adapted to the new conditions, but some older individuals survive by random chance. Senescence can eliminate those from the genetic pool. Even though individual selection forces always win over group selection ones, it is not exactly the individual that is selected, but its lineage. While senescence damages the individuals and has an evolutionary cost, it has a benefit of its own. It allows each lineage to adapt faster to changing conditions. We age because the world changes.Comment: 19 pages, 4 figure

The co‐evolution of longevity and social life

Living in social groups could influence the evolution of senescence and longevity by affecting key life‐history parameters such as extrinsic mortality and the cost of reproduction. For example, a decrease in extrinsic mortality as a result of social life is predicted to lead to the evolution of increased longevity. We argue that benefits of social life in terms of increased survival are common only in species in which life in large groups is already the norm, most likely because these species have adapted to depend on social groups. By contrast, species with smaller social groups tend to show no clear association between survival and social group size. This lack of a consistent benefit of social life on survival casts doubt on the idea that extended longevity should follow the evolution of sociality. In line with this, most rigorous cross‐taxonomic studies failed to find an association between sociality and longevity, suggesting that a social mode of life does not systematically lead to the evolution of extended longevity. The only effect of sociality on longevity that has been convincingly demonstrated is increased longevity in high‐ranking individuals from cooperatively breeding vertebrates and social insects, who benefit from the protection and support of their non‐breeding helpers. In contrast, helpers in these species usually do not show evidence of increased longevity, with the exception of naked mole rats where both breeders and helpers live much longer than related solitary species. Where long‐lived phenotypes exist in highly social species, such as social insect queens and naked mole rats, the scale of longevity increase is often striking. The means by which increased longevity is achieved are still poorly understood, but both social and physiological mechanisms are involved in reducing the burden of disease, including cancer, thus increasing the chances of surviving to old age

Pregnancy and infection [letter]

Pregnant women have an increased severity of infections with some organisms, including influenza virus, hepatitis E virus, herpes simplex virus, and malaria parasites. This review includes an update on immunologic alterations during pregnancy

FHIR-DHP: A standardized clinical data harmonisation pipeline for scalable AI application deployment

Background Increasing digitalisation in the medical domain gives rise to large amounts of healthcare data which has the potential to expand clinical knowledge and transform patient care if leveraged through artificial intelligence (AI). Yet, big data and AI oftentimes cannot unlock their full potential at scale, owing to non-standardised data formats, lack of technical and semantic data interoperability, and limited cooperation between stakeholders in the healthcare system. Despite the existence of standardised data formats for the medical domain, such as Fast Healthcare Interoperability Resources (FHIR), their prevalence and usability for AI remains limited.Objective We developed a data harmonisation pipeline (DHP) for clinical data sets relying on the common FHIR data standard.Methods We validated the performance and usability of our FHIR-DHP with data from the MIMIC IV database including > 40,000 patients admitted to an intensive care unit.Results We present the FHIR-DHP workflow in respect of transformation of “raw” hospital records into a harmonised, AI-friendly data representation. The pipeline consists of five key preprocessing steps: querying of data from hospital database, FHIR mapping, syntactic validation, transfer of harmonised data into the patient-model database and export of data in an AI-friendly format for further medical applications. A detailed example of FHIR-DHP execution was presented for clinical diagnoses records.Conclusions Our approach enables scalable and needs-driven data modelling of large and heterogenous clinical data sets. The FHIR-DHP is a pivotal step towards increasing cooperation, interoperability and quality of patient care in the clinical routine and for medical research

Exact Solution of an Evolutionary Model without Ageing

We introduce an age-structured asexual population model containing all the relevant features of evolutionary ageing theories. Beneficial as well as deleterious mutations, heredity and arbitrary fecundity are present and managed by natural selection. An exact solution without ageing is found. We show that fertility is associated with generalized forms of the Fibonacci sequence, while mutations and natural selection are merged into an integral equation which is solved by Fourier series. Average survival probabilities and Malthusian growth exponents are calculated indicating that the system may exhibit mutational meltdown. The relevance of the model in the context of fissile reproduction groups as many protozoa and coelenterates is discussed.Comment: LaTeX file, 15 pages, 2 ps figures, to appear in Phys. Rev.