We discuss pathological epigenetic events that are reversible (PEERs). A recent study by Poganik and colleagues showed that severe stress in mice and humans transiently elevates biological age of several tissues, and this transient age increase is reversible when the stress is removed. These studies suggest new strategies for reversing normal aging. However, it is important to note that developmental origin of health and disease studies have shown that developmental exposure to toxic chemicals such as lead causes permanent changes in neuron shape, connectivity and cellular hyperplasia of organs such as the heart and liver. In this review, the PEER hypothesis speculates that the hallmarks of aging and the hallmarks of developmental origin of health and disease intersect at PEERs.
Keywords: DOHaD; aging; developmental toxicity; epigenetic reprogramming; epigenomics; heterochronic parabiosis.
The main goal in aging research is to find treatments to reverse aging. There are nine hallmarks of aging which describe cellular mechanisms that change as we age. For example, one of the hallmarks of aging is cellular senescence, which means that cells stop dividing when they get old. In this review, we describe nine hallmarks of developmental origins of health and disease (DOHaD). DOHaD studies show that exposures of the mother during pregnancy to stress or toxic chemicals can alter the health of the child throughout the child's lifespan. We argue that six of the nine hallmarks of DOHaD overlap with the hallmarks of aging and are reversible by dietary restriction or by drugs such as rapamycin which affect nutrient signaling. Based on this finding, we have formulated a hypothesis that we call ‘pathological epigenetic events that are reversible’ that contain the six hallmarks that overlap between the hallmarks of aging and the hallmarks of DOHaD. With this unexpected connection between aging and DOHaD, we argue that findings in one field, such as drugs that reverse aging, can apply to treatments in the other field, such as ways to reverse the adverse effects of exposures during pregnancy.