“My SPARK project aims to uncover how DNA modifications drive immune system decline with age. I will use cutting-edge technology to analyze T cell alterations across diverse age groups, ultimately revealing strategies to enhance immune function and prevent age-related diseases.”
Is the decline of immunity with age written in our DNA?
Imagine our immune system as a powerful army, always on alert, ready to fight off infections and destroy harmful cells, like cancer. One key soldier in this army is the CD8+ T cell—its job is to hunt down and kill infected or cancerous cells. However, as we get older, this soldier becomes less effective. In fact, research shows that by the time people reach their 60s, about 64 percent of these CD8+ T cells are damaged and don’t function as well as they used to.
One of the reasons for this decline is a phenomenon called chronic inflammation, often driven by constant infections. A particularly interesting culprit is cytomegalovirus (CMV), a common virus that most of us carry. CMV normally stays dormant, but it can “wake up” as we age and cause low-level inflammation that wears down our immune system. However, new research suggests CMV might not actually be a primary cause of immune decline. Instead, it could be a symptom of something deeper and more mysterious happening inside our own bodies.
So, where is the real enemy? Is it external viruses like CMV, or could the real threat come from within our own DNA?
I believe the real problem might be Human Endogenous Retroviruses (HERVs)—ancient virus sequences that became part of our DNA millions of years ago, passed down from our ancestors. These viral “fossils” make up about 8 percent of our genome. For the longest time, HERVs were thought to be inactive in healthy individuals, but recent discoveries suggest that these viral sequences also “wake up” as we age.
With my SPARK project, I will investigate whether the key to this awakening lies in chemical modifications in our DNA—tiny molecular switches that control which genes are turned on or off. As we get older, these switches become unbalanced, potentially triggering the reactivation of HERVs. Once reactivated, these HERVs may cause chronic inflammation, leading to CD8+ T cell dysfunction. I aim to explore this hypothesis by using a cutting-edge tool called long-read sequencing to detect full-length viral RNA and DNA, including all the modifications that might be driving this process. The potential impact of this research could reveal that the virus fossils in our own DNA are contributing to age-related or even sex-based immune system decline. Ultimately, this research could even lead to new therapies. By repurposing drugs used to control DNA modifications and treatments already developed for retroviruses, we might be able to slow down or even reverse immune decline as we age.