Age Management Medicine News: October/November 2022 – #5

Oct. 14, 2022 (www.medicalnewstoday.com) – In 1952, Nobel-prize winner Dr. Peter Medawar put forward the hypothesis that aging processes may be a result of evolution’s natural selection not having that much to say about people past their child-bearing years.

A new study finds fresh support for Medawar’s hypothesis in an analysis of how roughly 20,000 human genes are expressed as we age.

The study suggests that our genes are less of an influence as we get older.

Study senior author Dr. Peter Sudmant, assistant professor in integrative biology at the University of California Berkeley tells Berkeley News, “Almost all human common diseases are diseases of aging: Alzheimer’s, cancers, heart disease, diabetes.”

“Massive amounts of public resources have gone into identifying genetic variants that predispose you to these diseases. What our study is showing is that, well, actually, as you get older, genes kind of matter less for your gene expression,” says Sudmant.

The study is published in Nature Communications.

Evolutionary logic

Dr. Sudmant summarized Medawar’s hypothesis for Medical News Today:

“Genes that are turned on when we are young are more constrained by evolution because they are critical to making sure we survive to reproduce, while genes expressed after we reach reproductive age are under less evolutionary pressure.”

Dr. Giuseppe Passarino, professor of genetics at the University of Calabria in Italy, who was not involved in the study, explained to MNT how this works:

“It is evident that in order to have more children, you need to survive and to be fit [long enough to] reproduce yourself. To get this goal, you need to have no diseases while you are young, to be able to find food, to get a partner.”

“Genes which are expressed during the first part of your lifetime are highly selected, and then only the best ones survive.”
— Dr. Giuseppe Passarino

“Evolution is based on the fact that individuals who have better fitness have more children. Thus, their genotypes will spread in the population more than those of subjects who have [fewer] children,” Dr. Passarino added.

Five problematic tissues

The researchers retrieved gene expression data for 27 different types of body tissues in almost 950 people from the GTEx web portal. Individuals were categorized as “young” if they were less than 55 years of age, and “old” if they were 55 or over.

In their analysis, the researchers found that genetics exerts about the same amount of influence over gene expression in almost all of our tissues until we cross into the “old” bracket.

At that point, aging plays a much more influential role for five critical tissue types — blood, colon, arteries, esophagus, and fat tissues — than does genetics.

As an influence on gene expression in the study, “aging” refers to the universal, progressive cellular aging processes associated with advancing years.

“In our study, we found in five high proliferation tissues (blood, colon, etc.), [that] these highly constrained genes are actually turned on late in life. These genes tend to be those that are involved in cell division and proliferation, and consequently, in cancer.”
— Dr. Peter Sudmant

How our environment affects our aging

While it would theoretically be helpful if evolution would help select genes that keep us healthy even after we reproduce, according to Dr. Sudmant:

“The ‘limit of evolution’ here is that, late in life, you really should not have these sorts of genes turned on, and having them turned on actually makes you susceptible to cancer. However, because these are cell types in your body that need to keep turning over — blood! — there is no other option.”

Hence, aging and environmental factors are more influential in gene expression for these critical tissues.

In the study, environmental influences include factors not directly associated with those processes: the quality of the air and water we breathe and eat, our diet, and also our level of physical exercise.

The study finds that environmental factors account for about a third of gene expression in older people.

“This [study] does not imply that genetics is not important for aging. There are many studies showing that the similarities between relatives regarding the quality of aging (presence of diseases or inabilities) are very high. In fact, although the genes expressed later in life are not selected, still they are important for our life.”
— Dr. Giuseppe Passarino

“In other words, we are equipped with highly selected alleles for the first part of our life and with alleles [that] are less selected for the second part. However, in both cases, our phenotype is based on our genes,” Dr. Passarino added.

What this study means

According to Dr. Passarino, to better understand the complexity of how humans age and to learn how to slow down this process, researchers need to study the genes expressed later in life and improve them.

“One option may be to see how the genetic machinery works in long-lived subjects, and try to modulate the machinery of others accordingly,” said Dr. Passarino.

”For instance, it has been observed that long-lived subjects have limited ability to use proteins or sugar. Thus, we can use a limited amount of proteins and sugar to modulate our organism machinery as if we were equipped with the same genes of long-lived subjects,” he elaborated.

“When we do studies to identify the genetics underlying disease, we often end up with many genes that we could potentially target. Our study now quantifies how age impacts the expression of genes in the population. We argue that age-associated genes might be better therapeutic targets than the ones that vary in their expression as a function of human genetics,” Dr. Sudmant said.

“We think that genes that show consistence in age-associated changes in expression in humans are potentially really interesting targets to follow up on!” he concluded.