Document text
Principal Investigator: OLIVER J RANDO
Organization: UNIV OF MASSACHUSETTS MED SCH WORCESTER
Fiscal Year: 2024
Award: $508,917
Funding agency: National Institute on Aging
Project Summary/Abstract
Over the past century, a marked demographic shift in the United States and other
wealthy countries has lead to childbearing occurring later and later in life. In addition to
the decrease in fecundity that accompanies aging, there is accumulating evidence that
paternal age can impact offspring health and disease. This has typically been attributed
to the effects of advanced paternal age on genetic changes in sperm that are transmitted
to children. Here, we consider an underappreciated possibility – that the aging process
affects epigenetic information carried in sperm, with resulting “epimutations” being
responsible for the altered phenotypes that manifest in the next generation.
Here, we propose to investigate the effects of aging on key male reproductive
tissues, including the testis, epididymis, seminal vesicle, and prostate. We will explore
the effects of advanced paternal age on a variety of behavioral and metabolic traits in
offspring, and will comprehensively analyze molecular differences between sperm
obtained from young and old animals.
Together, these experiments systematically address the effects of aging on male
reproductive function and on future generations, and may provide therapeutic avenues
for mitigating the effects of delayed paternity on disease risk in children.
Terms: <0-11 years old><21+ years old><Address><Adult><Adult Human><Affect><Age Months><Aging><Animals><Behavior><Behavioral><Body Tissues><Caloric Restriction><Cell Body><Cell Function><Cell Physiology><Cell Process><Cells><Cellular Function><Cellular Physiology><Cellular Process><Child><Child Youth><Children (0-21)><Conceptions><Country><Couples><Cytosine><Data Set><Development><Disease><Disorder><Elderly><Epididymis><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Fecundability><Fecundity><Female><Fertility><Fertilized Egg><Fertilized Ovum><Follow-Up Studies><Followup Studies><Foundations><Future><Future Generations><Gene Transcription><Genes><Genetic Alteration><Genetic Change><Genetic Transcription><Genetic defect><Germ Lines><Goals><Health><Histologic><Histologically><Histones><Human><Inbred Mouse><Individual><Intermediary Metabolism><Intervention><Intervention Strategies><Lead><Life><Life Style><Lifestyle><Measurement><Metabolic><Metabolic Processes><Metabolism><Methylation><Mice><Mice Mammals><Modeling><Modern Man><Molecular><Mouse Strains><Murine><Mus><Mutation><Neural Development><Neurodevelopmental Disorder><Neurological Development Disorder><Non-Polyadenylated RNA><Partner in relationship><Paternal Age><Pb element><Phenotype><Population><Pre-implantation Embryo Development><Pre-implantation development><Preimplantation Embryo Development><Preimplantation development><Prevalence><Prostate><Prostate Gland><Prostatic Gland><Public Health><RNA><RNA Expression><RNA Gene Products><RNA Seq><RNA sequencing><RNAseq><Reproductive Biology><Resolution><Ribonucleic Acid><Risk><Seminal Sacs><Seminal Vesicles><Sperm><Spermatozoa><Subcellular Process><Survey Instrument><Surveys><Testicles><Testis><Therapeutic><Time><Tissues><Transcription><Transmission><United States><Western World><adulthood><advanced age><age associated alterations><age associated changes><age associated effects><age correlated alterations><age correlated changes><age dependent alterations><age dependent changes><age effect><age related alterations><age related changes><age related effects><age specific alterations><age specific changes><aged animal><aged animals><aging effect><aging process><alterations with age><animal old age><bear children><bearing children><behavior phenotype><behavioral phenotyping><caloric restricted><calorically restricted><calorie restricted><calorie restriction><career><cell type><changes with age><child bearing><childbearing><developmental><disease risk><disorder risk><elderly animal><epigenetically><epigenome><epigenomics><experiment><experimental research><experimental study><experiments><father role><genital tract><genome mutation><genome wide analysis><genome wide studies><genome-wide analysis><genome-wide identification><genomic platform><geriatric><heavy metal Pb><heavy metal lead><impact of age><influence of age><innovate><innovation><innovative><interventional strategy><juvenile animal><kids><male><mate><metabolic phenotype><metabotype><neurodevelopment><neurodevelopmental disease><neuropsychiatric disease><neuropsychiatric disorder><next generation><offspring><old animals><older men><paternity><reproductive><reproductive function><reproductive tract><resolutions><scRNA-seq><senior citizen><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell genomics><single cell transcriptomic profiling><single-cell RNA sequencing><sperm cell><trait><transcriptome sequencing><transcriptomic sequencing><transmission process><young animal><youngster><zoosperm><zygote>