Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body mass, we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified five genes, important for tumor suppression, adaptive immunity, metastasis, and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of approximately 1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel ape-specific enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus. In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates

Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body mass, we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified five genes, important for tumor suppression, adaptive immunity, metastasis, and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of approximately 1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel ape-specific enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus. In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates

Human Ageing Genomic Resources:updates on key databases in ageing research

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).</p

Human Ageing Genomic Resources:updates on key databases in ageing research

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).</p

Cancer survival in the elderly: Effects of socio-economic factors and health care system features (ELDCARE project)

The purpose of the ELDCARE project is to study differences in cancer survival for elderly patients by country, taking into account the socio-economic conditions and the characteristics of health care systems at the ecological level. Fifty-three European cancer registries, from 19 countries, participating in the EUROCARE 3 programme, collected information to compute relative survival on patients aged 65-84 years, diagnosed over the period 1990-1994. National statistics offices provided the macro-economic and labour force indicators (gross domestic product, total health expenditure, and proportion of people employed in the agriculture sector) as well as the features of national health care systems. Survival for several of the cancer sites had high positive Pearson's correlations (r) with the affluence indicators (usually r > 0.7), but survival for the poor prognosis cancers (lung, ovary, stomach) and for cervix uteri was not so well correlated. Among the medical resources considered, the number of computed tomography scanners was the variable most related to survival in the elderly; the number of total health practitioners in the country did not show any relationship. Survival was related to the marital status of elderly women more strongly than for men and younger people. The highest correlations of survival with the percentage of married elderly women in the population were for cancers of the rectum (r = 0.79) and breast (r = 0.66), while survival correlated negatively with the proportion of widows for most cancers. Being married or widowed is for elderly people, in particular elderly women, an important factor influencing psychological status, life habits and social relationships. Social conditions could play a major role in determining health outcomes, particularly in the elderly, by affecting access to health care and delay in diagnosis

POTENTIAL EFFECTS OF WHOLE-BODY VIBRATION EXERCISES ON BLOOD FLOW KINETICS OF DIFFERENT POPULATIONS: A SYSTEMATIC REVIEW WITH A SUITABLE APPROACH

Background: The ability to control skin blood flow decreases with advancing age and some clinical disorders, as in diabetes and in rheumatologic diseases. Feasible clinical strategies such as whole-body vibration exercise (WBVE) are being used without a clear understanding of its effects. The aim of the present study is to review the effects of the WBVE on blood flow kinetics and its feasibility in different populations. Material and Methods: The level of evidence (LE) of selected papers in PubMed and/or PEDRo databases was determined. We selected randomized, controlled trials in English to be evaluated. Results: Six studies had LE II, one had LE III-2 and one III-3 according to the NHMRC. A great variability among the protocols was observed but also in the assessment devices; therefore, more research about this topic is warranted. Conclusion: Despite the limitations, it is can be concluded that the use of WBVE has proven to be a safe and useful strategy to improve blood flow. However, more studies with greater methodological quality are needed to clearly define the more suitable protocols