A new model of aging takes into account not only genetic factors and environmental exposures but also small changes that arise randomly at the cellular level.
The new model of aging takes into account not only genetic factors and environmental exposures but also small changes that arise randomly at the cellular level.
University Professor Caleb Finch introduced the “Triple Aging Phenotype” as a new conceptual paradigm that addresses the cause of age differences so much, even among identical human twins that share the same genes. Finch noted that only about 10 to 35 percent of longevity can be traced back to genes inherited from our parents.
Finch authored the paper in which he presented the model with a former graduate student, Amin Haqqani, who received his PhD in Aging Biology from the USC Leonard Davis School in 2020 and is now a postdoctoral researcher at UCLA. In the article, they suggested that the limited heritability of patterns of aging and longevity in humans is the result of interactions of the genetic environment, along with random, or chance, differences in the body’s cells. These random changes can include the cellular changes that occur during evolution, the molecular damage that occurs later in life, and more.
“We wanted to present a conceptual map and some new terminology that would stimulate a more comprehensive understanding of the limitations of genetic determinants in aging, and how important it is to consider genetic variation in the relationship to the environment, and to include this new field,” said Finch, who holds the ARCO / William F. Kieschnick Chair in the Neuroscience of Aging in USC Leonard Davis School, found that the random differences, which have been well recognized by the different fields. “They are not set in a formal context in which the full package can be discussed, and this is what I hope our article will achieve.”
The new paradigm is a natural extension of the idea of the show, which was first proposed by cancer epidemiologist Christopher Paul Wilde in 2005 to draw attention to the need for more data on lifetime exposure to environmental carcinogens. The display concept illustrates how external factors, from air pollution and socio-economic status to individual diet and exercise patterns, interact with intrinsic or intrinsic factors such as the body’s microbiome and fat deposits.
The presentation has now become a flagship model, transcending previous descriptions of environmental factors as influencing risks “one by one”. Finch previously expanded the concept of display by introducing Alzheimer’s disease detection. The gyro-exosome is now looking at how genes and the environment interact over a lifetime to shape how we age.
The new paradigm demonstrates that intracellular differences in gene expression, differences arising during evolution, random mutations, epigenetic changes – turning off genes or “turning them on” – must be viewed explicitly outside of traditional genetic or environmental research on aging, Finch said. A more detailed study of these shell processes has been enabled by cutting-edge research techniques, including the study of intracellular gene transcription in addition to ChIP sequencing, which can elucidate how individual proteins interact with DNA.
Effects of chance on health
In the paper, Finch and Hagany discuss several examples of how age-related disease risk is poorly predicted by DNA alone but strongly influenced by environmental exposures as well as the time and duration of exposure, including during development or over decades.
One well-known example of a gene linked to an increased risk of Alzheimer’s disease is ApoE-4. However, having the ApoE-4 gene does not conclusively mean that someone will develop Alzheimer’s disease. Studies in mice and humans revealed that ApoE-4 and groups of related genes interact with exposures such as air pollution or cigarette smoke to influence risk, and Alzheimer’s patients showed differences in epigenetic inheritance compared to individuals without the disease.
He added that the notion of environmental exposure could extend beyond what many people expect. Exposure to disease early in life can affect health risks later in life – and across generations.
He explained, “The environment that we are exposed to goes back to our grandmothers because the egg from which we came from was in our mothers’ ovaries at the time of her birth.” “That means, in my case, because my grandmother was born in 1878, I may have some traces from a nineteenth-century environment, which included a much greater exposure to infectious diseases due to the lack of antibiotics.”
Finch said he hopes the most comprehensive model of how genes, the environment, and random changes over time interact to affect aging will be a new debate about what the rapidly evolving field of precision medicine needs to consider to promote healthy aging.
“I think there will be much greater recognition in understanding individual patterns of aging,” he said. “We can only define it to a certain point through knowledge of genetic risks; we must have a more comprehensive understanding of exposures throughout the life, environments and lifestyles of an individual in order to better understand the genetic risks of specific diseases.”
”Interactions of gene, environment, and random variations in the Gero-ExposomeIt was published online in Gerontology Series A in February 2021. The research was supported by NIH Grants R01-AG051521, P50-AG005142, and P01-AG055367 to Finch and training support for Haghani via T32-AG052374.