ASRM Today: Genetics - Episode Six

Genetics and Aging: Let's unravel the science behind aging and explore whether genetics holds the key to a longer healthier future.

Welcome to ASRM Today, a podcast that takes a deeper dive into the current topics in reproductive medicine. This is ASRM Today. I'm your host, Jeffrey Hayes.

Today, we're tackling one of humanity's greatest mysteries, aging. Why do we age? Is there a genetic clock controlling the process? And could we use genetics to slow down or even reverse aging? Scientists are uncovering the secrets of longevity, from the role of telomeres in cellular damage to cutting-edge gene therapies that might one day extend human life. Let's unravel the science behind aging and explore whether genetics holds the key to a longer, healthier future.

Aging isn't just about getting wrinkles and gray hair. It's a biological process driven by genetics, cellular function, and environmental factors. But why do we age in the first place? Scientists have identified several key mechanisms behind aging.

First, telomere shortening. Telomeres are the protective caps on the ends of our chromosomes. Every time a cell divides, telomeres get shorter.

Eventually, they become too short to protect the DNA, leading to cell death. Second, DNA damage and mutations. Over time, our cells accumulate mutations due to environmental stressors like UV radiation, pollution, and even the normal wear and tear of life.

These mutations can lead to diseases like cancer. Third, cellular senescence. Some cells stop dividing and enter a quote, zombie state called senescence, where they don't function properly but also refuse to die.

These cells contribute to inflammation and aging-related diseases. Fourth, mitochondrial dysfunction. Mitochondria, the powerhouse of the cell, lose efficiency with age, leading to decreased energy production and increased oxidative stress, which damages cells.

So if aging is partly written in our genes, question is, can we rewrite the script? Why do some people live to 100 while others develop age-related diseases much earlier? Longevity genes play a crucial role. Studies of centenarians, people who live to 100 or older, show that many have genetic variants that protect them from aging-related diseases. One key player in that is the FOXO3 gene, linked to increased lifespan and resistance to cellular stress.

People with certain variants of the FOXO3 are more likely to live longer, healthier lives. Another fascinating discovery involves the sirtuins, a family of genes that regulate cellular health. Sirtuins help repair DNA, reduce inflammation, and improve mitochondrial function.

Resveratrol, a compound found in red wine, has been shown to activate sirtuins, leading to speculation that it might have anti-aging properties. So if some people are genetically wired to age more slowly, can we manipulate these genes to extend life? The idea of slowing or reversing aging sounds like science fiction, but researchers are already testing ways to do it using gene therapy. One promising approach involves telomerase activation.

Telomerase is an enzyme that can rebuild telomeres, potentially extending the lifespan of cells. In 2015, scientist Elizabeth Parrish underwent an experimental gene therapy to increase her telomerase levels. Early results showed promising effects on her biological markers of aging.

Another approach targets senescent cells, those zombie cells that build up with age. Scientists are developing drugs called senolytics, which selectively remove these dysfunctional cells, reducing inflammation and slowing aging. But while slowing aging is one thing, could we actually stop it or even reverse it? Some scientists believe that cellular reprogramming could one day reset aging cells to a more youthful state.

The idea is based on the Yamanaka factors, a set of four genes that could turn adult cells back into stem-like state. In 2021, researchers at Harvard successfully used this technique to reverse aging in mice. This raises the question, could similar therapies be used to rejuvenate human tissues? Companies like Altos Labs, backed by billionaires like Jeff Bezos, are investing heavily in cellular reprogramming research.

Will we see anti-aging treatments in our lifetime? The idea of extending human lifespan raises huge ethical questions. If people live to 150 or 200 years old, how will that affect population growth and resources? Will only the wealthy have access to life-extending treatments? Could an extended lifespan change the way we experience life, our careers, relationships, and sense of purpose? While we don't have all the answers yet, one thing is clear. Understanding the genetics of aging could help us lead longer, healthier lives, even if immortality remains a distant dream.

That's a wrap on today's episode. If you enjoyed this episode, subscribe and share it with friends. Until next time, I'm Jeffrey Hayes and this is ASRM Today.

This concludes this episode of ASRM Today. For show notes, author information, and discussions, go to asrmtoday.org. This material is copyrighted by the American Society for Reproductive Medicine and may not be reproduced or used without express consent from ASRM. ASRM Today series podcasts are supported in part by the ASRM Corporate Member Council.

The information and opinions expressed in this podcast do not necessarily reflect those of ASRM and its affiliates. These are provided as a source of general information and are not a substitute for consultation with a physician.