Genetics, Aging and Environment

 “Age is just a number and mine is unlisted,” says the actor in the TV commercial for the high protein nutritional drink. We age differently, so some might count age as only a number. But don’t rush to discount age. A recent study showed age often plays a greater role than genetics in gene expression and susceptibility to disease.

TV commercial in which actor says, “Age is just a number and mine is unlisted” (from www.ispot.tv/ad/nHX8/boost-high-protein-age-is-just-a-number).

Welcome back. Let me jump right in with the oldest evolutionary explanation for biological aging. On 6 December 1951, Peter Brian Medawar presented an inaugural lecture at University College, London, titled “An Unsolved Problem of Biology.” He proposed the mutation accumulation theory of aging.

Medawar’s theory is based on the idea that the force of natural selection ebbs with age as individuals are less likely to reproduce and contribute their genetic information to the next generation. As reproduction ceases, the weaker force of natural selection cannot consistently eliminate harmful mutations, which then accumulate and lead to the evolution of aging.

Genetics vs. Aging
Now, let me jump to the recent study I mentioned in the opening. A team of researchers affiliated with the University of California, both Berkeley and Los Angeles, investigated the relative effects of genetics, aging and environment on how some 20,000 human genes are expressed. The researchers built a statistical model using data on 27 different human tissues available from nearly 1,000 people. (If you’re feeling a bit lost about tissues and genes, “Tissues” under P.S. below might help.) 

Four types of tissue (graphic prepared by A.D.A.M Images; figure from medlineplus.gov/ency/imagepages/8682.htm).

The team found that genetics mattered about the same amount across the tissues, not playing more of a role in one tissue or another.

The impact of aging, however, varied more than twentyfold among the tissues. Whether blood, colon, arteries, esophagus or fat tissue, age plays a much stronger role than genetics in driving gene expression patterns.

Outlier Tissues
The researchers also found that Medawar’s theory did not hold for all 27 tissues. Evolutionary important genes were expressed at higher levels in older people in five types of tissues. What’s different about these tissues is that they constantly turn over throughout our lifespan. Because blood, for instance, has to proliferate for us to live, these genes have to be turned on late in life.

Every time these tissues replace themselves, they risk creating a genetic mutation that can lead to disease. And these five tissues do produce the most cancers.

Trends in Cancer: the evolution of lifespan and age-dependent cancer risk (from
www.cell.com/trends/cancer/fulltext/S2405-8033(16)30121-2). 

The study indirectly indicated the effect of environment--air, water, food, exercise; the impact of everything other than age and genetics. The researchers judged that environment accounts for up to one-third of the changes in gene expression with age.

Wrap Up
The results underscore that, while our genetic makeup can help predict gene expression when we are younger, it is less useful in predicting which genes are ramped up or down when we’re older (being older than 55 in the study). Identical twins have the same set of genes, yet as they age, their gene expression profiles diverge, and the twins can age very differently from one other.

The findings have implications for efforts to correlate diseases of aging with genetic variation. The study’s senior researcher suggests that perhaps these efforts should focus less on genetic variants that impact gene expression when pursuing drug targets.

So, give age due diligence, and thanks for stopping by.

P.S.
Mutation accumulation theory of aging
books.google.com/books/about/An_Unsolved_Problem_of_Biology.html?id=ozEmPQAACAAJ
en.wikipedia.org/wiki/Mutation_accumulation_theory
Study of tissue impacts of aging and genetics in Nature Communications journal: www.nature.com/articles/s41467-022-33509-0
Article on study on EurekAlert! website: www.eurekalert.org/news-releases/967253

Tissues (from medlineplus.gov/ency/imagepages/8682.htm and training.seer.cancer.gov/anatomy/cells_tissues_membranes/tissues/)
Cells are the building blocks of all living things, and genes are inside almost every cell in our bodies. Tissues are groups of cells that have similar structure and that function together as a unit. There are four basic types of tissue: connective tissue supports other tissues and binds them together (bone, blood and lymph tissues); epithelial tissue provides a covering (skin, the linings of passages inside the body); muscle tissue includes striated muscles that move the skeleton and smooth muscle, such as the muscles that surround the stomach; nerve tissue is made up of nerve cells (neurons) and carry "messages" to and from parts of the body.