Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle

Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse “ages” the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world’s countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome

Generation 4.2 (Gen 4 repeated)

Each row represents sequential mass measurements for a given individual. The column headings, in order, represent the beetled identification number (ID), its sex (Sex), the sire that produced it (Sire), the dam that produced it (DAM), the date of its egg hatch (HatchDate), the date of the first measurement (Date1), the age at first measurement (DSH1), the mass at first measurement (Mass1), the date of second measurement (Date2), etc. After larval measurements, information about the pupal and adult stages is listed in columns to the right: date of pupation (PubDate), age at pupation (DTP), pupal mass (PupMass), date of eclosion to the adult stage (EcDate), and age at eclosion to the adult stage (DTE). Any individuals who do not have a pupal mass measurement did not survive to pupation, and individuals without an eclosion date (but with a pupal mass measure) survived to pupation but not to eclosion

Data from: Artificial selection on larval growth curves in Tribolium: correlated responses and constraints

Body size is often constrained from evolving. Although artificial selection on body size in insects frequently results in a sizable response, these responses usually bear fitness costs. Further, these experiments tend to select only on size at one landmark age, rather than selecting for patterns of growth over the whole larval life stage. To address whether constraints may be caused by larval growth patterns rather than final size, we implemented a function-valued (FV) trait method of selection, in which entire larval growth curves from Tribolium were artificially selected. The selection gradient function used was previously predicted to give the maximal response and was implemented using a novel selection index in the FV framework. Results indicated a significant response after one generation of selection, but no response in subsequent generations. Correlated responses included increased mortality, increased critical weight, and decreased development time (DT). The lack of response in size and development time after the first generation was likely caused by increased mortality suffered in selected lines; we demonstrated that the selection criterion caused both increased body size and increased mortality. We conclude that artificial selection on continuous traits using FV methods is very efficient and that the constraint of body size evolution is likely caused by a suite of trade-offs with other traits

Geneartion 4

Each row represents sequential mass measurements for a given individual. The column headings, in order, represent the beetled identification number (ID), its sex (Sex), the sire that produced it (Sire), the dam that produced it (DAM), the date of its egg hatch (HatchDate), the date of the first measurement (Date1), the age at first measurement (DSH1), the mass at first measurement (Mass1), the date of second measurement (Date2), etc. After larval measurements, information about the pupal and adult stages is listed in columns to the right: date of pupation (PubDate), age at pupation (DTP), pupal mass (PupMass), date of eclosion to the adult stage (EcDate), and age at eclosion to the adult stage (DTE). Any individuals who do not have a pupal mass measurement did not survive to pupation, and individuals without an eclosion date (but with a pupal mass measure) survived to pupation but not to eclosion

Data from: Constraints on the evolution of function-valued traits: a study of growth in Tribolium castaneum

Growth trajectories often impact individual fitness. They are continuous by nature and so are amenable to analysis using a function-valued (FV) trait framework to reveal their underlying genetic architecture. Previous studies have found high levels of standing additive genetic (co)variance for growth trajectories despite the expectation that growth should be responding to frequent strong directional selection. In this study, the FV framework is used to estimate the additive genetic covariance function for growth trajectories in larval Tribolium castaneum to address questions about standing additive genetic (co)variance and possible evolutionary constraints on growth and to predict responses to four plausible selection regimes. Results show that additive genetic (co)variance is high at the early ages, but decreases towards later ages in the larval period. A selection gradient function of the same size and in the same direction of the first eigenfunction of the G-function should give the maximal response. However, evolutionary constraints may be acting to keep this maximal response from being realized, through either conflicting effects on survivability and fecundity of larger body size, few evolutionary directions having sufficient additive variance for a response, genetic trade-offs with other traits or physiological regulatory mechanisms. More light may be shed on these constraints through the development of more sophisticated statistical approaches and implementation of additional empirical studies to explicitly test for specific types of constraints

Tribolium Larval Mass Data

The file gives mass measurements for individuals who are listed in rows. The first three columns list identifying information for each larva; the first column gives the ID number, the second gives the sire number, and the third gives the dam number. The fourth column gives the hatch date, from which each 'age' is measured. From here, each data entry takes three columns: one for date of measurement, one for days since hatch (or, age at measurement), and one for the actual mass measurement (which is in grams). The numbers following the headings in this column represent the number of each measurement (i.e. 'mass5' indicates the fifth mass measure). Data concerning the pupal stage begin at the 44th column. The first three columns are the date of pupation, pupation age, and pupal mass. The 47th column indicates the sex of the individual, with 1 representing a male and 0 representing a female. The last two columns indicate the date and age of eclosion to the adult stage, respectively. Any blank entries represent a lack of data points either for that measurement or for that identifying information

Generation 3

Each row represents sequential mass measurements for a given individual. The column headings, in order, represent the beetled identification number (ID), its sex (Sex), the sire that produced it (Sire), the dam that produced it (DAM), the date of its egg hatch (HatchDate), the date of the first measurement (Date1), the age at first measurement (DSH1), the mass at first measurement (Mass1), the date of second measurement (Date2), etc. After larval measurements, information about the pupal and adult stages is listed in columns to the right: date of pupation (PubDate), age at pupation (DTP), pupal mass (PupMass), date of eclosion to the adult stage (EcDate), and age at eclosion to the adult stage (DTE). Any individuals who do not have a pupal mass measurement did not survive to pupation, and individuals without an eclosion date (but with a pupal mass measure) survived to pupation but not to eclosion