Aging Nature Vs. Nurture: Study Finds That Your Environment Affects Aging More Than Your Genes?
Are we born predisposed to how we will age, or do your environment and decisions — what you eat and drink, how much you sleep and stress out, whether you exercise or smoke — dictate the quality of aging?
A study from the University of California Berkeley finds that, as we get older, our genetics play a lesser role in how our genes function. Instead, the research team thinks that how our genes work as we get older is more affected by our decisions.
“What our study is showing is that, well, actually, as you get older, genes kind of matter less for your gene [activity],” said Peter Sudmant, UC Berkeley assistant professor of integrative biology and a member of the campus’s Center for Computational Biology. “And so, perhaps, we need to be mindful of that when we're trying to identify the causes … of aging.”
Our survival requires the nuts and bolts of our cell’s processes to operate with the utmost precision. But as individuals age, many core cell processes deteriorate, resulting in impaired function and disease. What influences these processes? Are we born with a set timer for aging? Or does our environment have a more significant effect on how we age?
Peter B. Medawar developed a theory on aging in the 1940s based on two concepts. First, most species in the wild die from predators, infections, and accidents rather than from aging-related illnesses. Thus there is a low likelihood that an individual will still be alive and able to reproduce at a ripe old age. Second, because natural selection becomes weaker with age, it ignores the performance of people who are getting older. As a result, when these impacts manifest at advanced ages, selection cannot favor positive or mitigate adverse effects.
Accordingly, Medawar reasoned that carriers of the unfavorable mutation would have passed it on to the next generation before the damaging late-life effects would become apparent if the effects of a deleterious mutation were limited to late ages when reproduction has primarily ceased, and future survival is unlikely. Natural selection would struggle to remove such a mutation in this case. Throughout evolution, these ineffective mutations would accumulate in the population through genetic drift, eventually resulting in the evolution of aging.
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So, what does the data show? How do your genetics influence who you are, your characteristics, such as your height and weight, and whether you have heart disease?
There's been a lot of work done in human genetics to understand how genes are turned on and off by human genetic variation. Interestingly, studies of identical twins have shown that there are quite a few differences in gene activity as the siblings age, suggesting that there is a role for the environment in modulating gene activity with age and that this is not strictly regulated by genetics. However, a key challenge remains in quantifying age-associated changes in biological processes across tissues and identifying how genetic variation influences such changes.
The UC Berkeley research team set out to understand how aging affects gene activity and to model the relative impact of time and genetic variation on age-associated changes across tissues. The first result the UC Berkeley research team found was that your genetics matter less the older you get. “What our study is showing is that, well, actually, as you get older, genes kind of matter less for your gene [activity],” said Sudmant. “While young individuals are closer together in terms of gene [activity] patterns, older individuals are further apart. It’s like a drift through time as gene [activity] patterns become more and more erratic. And so, perhaps, we need to be mindful of that when we're trying to identify the causes … of aging.”
While this study corroborates the inverse relationship between age and the variability in gene activity as predicted by Medawar’s hypothesis, the UC Berkeley team also surprisingly identify five tissues that exhibit the opposite pattern. In these five tissues, age-associated signatures of increased cancer are enriched. “Across all the tissues in your body, genetics matters about the same amount. It doesn't seem like it plays more of a role in one tissue or another tissue,” he said. “But aging is vastly different between different tissues. In your blood, colon, arteries, esophagus, fat tissue, age plays a much stronger role than your genetics in driving your gene expression patterns.”
These results highlight the distinct evolutionary forces that act on late-acting genes expressed in highly proliferative cell types. “From an evolutionary perspective, it is counterintuitive that these genes should be getting turned on until you take a close look at these tissues,” Sudmant said. “I guess this tells us a little bit about the limits of evolution. Your blood, for instance, always has to proliferate for you to live, and so these super-conserved, very important genes have to be turned on late in life. This is problematic because it means that those genes are going to be susceptible to getting somatic mutations and getting turned on forever in a bad…way. So, it kind of gives us a little bit of a perspective on what the limitations of living are like. It puts bounds on our ability to keep living.”
Together, this study provides insights into tissue-specific aging patterns and the relative impact of genetics and aging on gene activity. The UC Berkeley researchers anticipate that future studies across tissues and cells of gene activity regulation will further elucidate how both programmed and reactive processes of aging drive human disease.
Yamamoto, R., Chung, R., Vazquez, J.M. et al. Tissue-specific impacts of aging and genetics on gene expression patterns in humans. Nat Commun 13, 5803 (2022). https://doi.org/10.1038/s41467-022-33509-0