Mounting evidence supports that our life experiences can influence the health and longevity of our descendants. For instance, analysis of three generations of family members in Overkalix, Sweden demonstrated a correlation between food availability to grandparents and health and mortality rates in their grandchildren. Moreover, multiple studies in rodents have linked parental treatment regimes, such as diet and stress, with changes in offspring metabolism and behavior. Despite a wealth of evidence that paternal environment can influence offspring health, how such “transgenerational” inheritance is mediated remains mysterious. Determining the mechanisms of transgenerational inheritance has important implications for public health and policy. Many common metabolic diseases, such as diabetes, have both genetic components and contributions from a patient's lifestyle and environment. Only a fraction of the heritability of such diseases can be explained by genetic variation; instead, it is now increasingly appreciated that epigenetic (non-DNA sequence-based) inheritance likely contributes to such diseases. This proposal aims to provide the first deep understanding of the key steps of transgenerational inheritance of the father’s life experiences and environment.
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