This Study Reveals Why Genetics Won’t Save you from the Diseases of Aging | Why Identical Twins Age Differently

A New Study on Genes and Longevity

A new study from the University of California has provided critical insights into the role of genetics in aging and longevity. Published in Nature Communications, the research focuses on how gene expression changes over time and suggests that environmental factors may have a greater influence on aging than genetics, especially concerning age-related diseases like diabetes and cancer.

While there has been extensive research on how genetics shape the aging process, this UC Berkeley study reveals that genetic differences play a diminishing role as individuals grow older. Instead, the environment appears to take precedence, driving significant changes in gene expression as people age.

The Study

Researchers analyzed the combined impact of genetics, aging, and the environment on the expression of 20,000 human genes. They discovered that, as people age, environmental factors and the aging process become more critical in shaping gene expression than genetic variation. The way genes are expressed—meaning how actively they function—governs key biological processes, including hormone regulation, metabolism, and enzyme activity essential for bodily repair.

Assistant Professor Peter Sudmant of UC Berkeley explained the purpose of the research: "How do your genetics—what you got from your sperm donor and your egg donor and your evolutionary history—influence who you are, your phenotype, such as your height, your weight, whether or not you have heart disease? There's been a huge amount of work done in human genetics to understand how genes are turned on and off by human genetic variation. Our project came about by asking, 'How is that influenced by an individual's age?' And the first result we found was that your genetics actually matter less the older you get."

Genes Matter Less with Age

The findings suggest that while genetic makeup can predict gene expression patterns early in life, its influence declines with age. For example, identical twins—who share the same DNA—show increasingly different gene expression profiles as they age, indicating that even individuals with identical genetic material can age in distinct ways.

The study has important implications for understanding age-related diseases. Professor Sudmant commented: "Such studies should perhaps focus less on genetic variants that impact gene expression when pursuing drug targets."

He further elaborated that, “Almost all human common diseases are diseases of aging: Alzheimer's, cancers, heart disease, and diabetes. All of these diseases increase their prevalence with age. 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. And so, perhaps, we need to be mindful of that when we're trying to identify the causes of these diseases of aging."

Medawar’s Hypothesis

These findings align with Medawar’s hypothesis, which posits that genes crucial for survival and reproduction are under strong evolutionary pressure, while genes expressed later in life face less constraint, resulting in greater variability.

Professor Sudmant explained that "We're all aging in different ways, while young individuals are closer together in terms of gene expression patterns, older individuals are further apart. It's like an uncontrolled drift through time as gene expression patterns become more and more erratic."

Study Size and Scope

This research is the first to examine both aging and gene expression across a broad range of tissues and individuals. Professor Sudmant and his team built a statistical model to assess the roles of genetics and aging across 27 different tissue types from nearly 1,000 individuals. The study revealed that the impact of aging varies widely—more than twentyfold—across tissues.

Professor Sudmant noted: "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. 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."

Medawar’s Hypothesis and Tissue Variability

While the study largely supports Medawar’s hypothesis, some surprising exceptions emerged. In five of the 27 tissue types studied, genes critical for evolutionary fitness were more active in older individuals. Sudmant explained: "From an evolutionary perspective, it is counterintuitive that these genes should be getting turned on, until you take a close look at these tissues. These five tissues happen to be the ones that constantly turn over throughout our lifespan and also produce the most cancers. Every time these tissues replace themselves, they risk creating a genetic mutation that can lead to disease."

The Role of the Environment

The research also highlights the significant role of environmental factors in aging. Environmental influences—including air and water quality, diet, and physical activity—account for up to one-third of the changes in gene expression with age. Sudmant emphasized the importance of these external factors: "The environment impacts aging by driving changes in gene expression beyond what can be explained by genetics alone."

The findings suggest that while genetics lay the foundation for early gene expression patterns, environmental factors and the natural aging process ultimately determine how individuals age and the health challenges they encounter later in life.

Study Links:

https://www.nature.com/articles/s41467-022-33509-0

https://www.biorxiv.org/content/10.1101/2021.11.16.468753v1

https://www.researchgate.net/publication/364114819_Tissue-specific_impacts_of_aging_and_genetics_on_gene_expression_patterns_in_humans