A new study by Yousefzadeh et al. sheds light on a long-held suspicion: DNA damage isn’t just a passenger on the aging train, it might be the driver. This research titled “DNA damage—how and why we age?“, and published in eLife Sciences, explores the intricate connections between DNA damage and the hallmarks of aging, building a strong case for DNA damage as a root cause.
As we age, our ability to bounce back from life’s challenges diminishes. This decline in resilience, termed homeostatic dysregulation, increases our susceptibility to illness and mortality. Scientists have been eyeing cellular damage, particularly DNA damage, as a potential culprit behind this decline.
Our DNA, the blueprint for a healthy cell, faces constant threats. Its very structure makes it vulnerable to errors during normal cellular processes and attacks from environmental toxins. All living things possess DNA repair mechanisms to combat this onslaught, but this defense system comes with a trade-off.
When DNA damage persists, a state called genotoxic stress, cells face a difficult choice. They can either undergo apoptosis (cellular suicide) to prevent a corrupted genome from replicating, or enter senescence, becoming inactive but not dying. While both options prevent damaged cells from dividing, they contribute to aging. Senescent cells, for instance, can secrete harmful substances that disrupt the surrounding tissue.
Yousefzadeh and his team (Chathurika Henpita, Rajesh Vyas, Carolina Soto-Palma, Paul Robbins, and Laura Niedernhofer) delve deeper into the evidence suggesting DNA damage isn’t just a consequence of aging, but a driving force. They explore how DNA damage intertwines with other hallmarks of aging, strengthening the case for it being the root cause.
One key connection lies within the mitochondria, the cell’s powerhouses. These organelles not only generate energy but also contribute to the production of free radicals that damage DNA. This damage can further impair mitochondrial function, creating a vicious cycle that accelerates cellular decline.
Genotoxic stress also disrupts protein homeostasis, the delicate balance between protein production and degradation. This can lead to the accumulation of misfolded proteins, another hallmark of aging.
Inflammation, a chronic low-grade battle within the body, also plays a role. DNA damage can trigger inflammatory pathways, and chronic inflammation can lead to further DNA damage, creating a self-perpetuating cycle of cellular dysfunction.
The intricate web connecting DNA damage to these other pillars of aging paints a compelling picture. It suggests that by mitigating DNA damage, we might be able to slow down or even prevent the relentless march of aging. The authors acknowledge the complexity of aging, but the evidence they present for DNA damage as a root cause is undeniable. Future research focused on protecting our genetic code has the potential to unlock a new era of healthy longevity.
