title: Pervasive Effects of Aging on Gene Expression in Wild Wolves.
abstract: Gene expression levels change as an individual ages and responds to environmental conditions. With the exception of humans, such patterns have principally been studied under controlled conditions, overlooking the array of developmental and environmental influences that organisms encounter under conditions in which natural selection operates. We used high-throughput RNA sequencing (RNA-Seq) of whole blood to assess the relative impacts of social status, age, disease, and sex on gene expression levels in a natural population of gray wolves (Canis lupus). Our findings suggest that age is broadly associated with gene expression levels, whereas other examined factors have minimal effects on gene expression patterns. Further, our results reveal evolutionarily conserved signatures of senescence, such as immunosenescence and metabolic aging, between wolves and humans despite major differences in life history and environment. The effects of aging on gene expression levels in wolves exhibit conservation with humans, but the more rapid expression differences observed in aging wolves is evolutionarily appropriate given the species' high level of extrinsic mortality due to intraspecific aggression. Some expression changes that occur with age can facilitate physical age-related changes that may enhance fitness in older wolves. However, the expression of these ancestral patterns of aging in descendant modern dogs living in highly modified domestic environments may be maladaptive and cause disease. This work provides evolutionary insight into aging patterns observed in domestic dogs and demonstrates the applicability of studying natural populations to investigate the mechanisms of aging.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles.
authors.forename: Pauline
authors.initials: P
authors.lastname: Charruau
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Johnston
authors.affiliation: Yellowstone Center for Resources, National Park Service, Yellowstone National Park.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Stahler
authors.affiliation: Department of Biology, Duke University.
authors.forename: Amanda
authors.initials: A
authors.lastname: Lea
authors.affiliation: Department of Evolutionary Anthropology, Duke University.
authors.forename: Noah
authors.initials: N
authors.lastname: Snyder-Mackler
authors.affiliation: Yellowstone Center for Resources, National Park Service, Yellowstone National Park.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Smith
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University.
authors.forename: Bridgett M
authors.initials: BM
authors.lastname: vonHoldt
authors.affiliation: Department of Medicine, University of California, Los Angeles Cousins Center for Psychoneuroimmunology, Semel Institute, University of California, Los Angeles.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
authors.affiliation: Department of Biology, Duke University Department of Evolutionary Anthropology, Duke University.
authors.forename: Jenny
authors.initials: J
authors.lastname: Tung
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles rwayne@biology.ucla.edu.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Wayne
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics*; D000818:Animals; D000835:Animals, Wild; D005075:Biological Evolution; D004285:Dogs; D004777:Environment; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D008297:Male; D010802:Phylogeny; D012641:Selection, Genetic; D017423:Sequence Analysis, RNA / Q000379:methods; D012737:Sex Factors; D019596:Wolves / Q000235:genetics*
keywords: Canis lupus; RNA-Seq; canid; immunosenescence; senescence; transcriptome