Research Highlight October 10, 2017

What happens to the immune symphony as we age?

What happens to the immune symphony as we age?

There’s no getting around it — we all age, and as we age our health declines. This is due in part to the decline of the immune system, our primary protection against pathogens (viruses, bacteria) and even cancer cells, making us more susceptible to infection and diverse diseases. And as we age we respond less well to vaccinations and other preventive measures.

Why do these changes take place? The challenge mostly lies in understanding how cells in our body (including the ones that form the immune system) function, a highly complex process that is precisely orchestrated through regulatory mechanisms.

The healthy functioning of a cell is like a symphony orchestra conducted to perfection. But with aging, this orchestra starts losing its precision and the performance goes haywire. In “The chromatin accessibility signature of human immune aging stems from CD8+ T cells,” a paper published in The Journal of Experimental Medicine, a research team led by Professor Jacques Banchereau, Ph.D.Uses genomic tools to characterize human immunity in both healthy and disease states.Jacques Banchereau, Ph.D., and Assistant Professor  Exploring the science of agingJAX computational scientist Duygu Ucar bridges the worlds of biology and computer science to unlock the secrets of aging and age-related disease.Duygu Ucar, Ph.D., of The Jackson Laboratory, and George Kuchel, M.D., of the UConn Aging Center, has used advance genomic profiling techniques to uncover a distinctive genomic pattern associated with aging of the immune system.

The collaborative, multidisciplinary team of immunologists, computational scientists and a clinician partner collected and profiled blood samples from 28 young (ages 22-40) and 21 elderly (age 65 and over) volunteer subjects, and isolated immune cells from the blood, including monocytes, B cells and T cells. They investigated how the immune cells’ epigenomes — the layers of information that surround DNA and help determine when and where different genes get activated — change with aging,

Epigenomic patterns established in a cell play the major role in the precise orchestration of the cellular symphony. Furthermore, these patterns are highly dynamic and can provide the plasticity that cells need to respond to infections and other cellular challenges.  This study uncovered that with aging, epigenetic patterns of immune cells significantly change; as a consequence, certain parts of our genome are silenced or activated as we age.

The team further described that the silencing associated with aging is specifically observed in genes involved in T cell signaling, particularly with the IL-7 signaling pathway. A signature that reliably distinguished elderly from young samples thus provides a possible biomarker for reduced immune functions and potential therapeutic targets to boost immune responses. Further profiling of T cells by the team revealed that this signature arises specifically from a subset of T cells, CD8+ (or killer) T cells, which are also the predominant cells in most cancer immunotheraphy studies, since they can kill the cancer cells.  

Moving forward, the team is looking forward to conducting longitudinal studies to track aging-related changes over time. Conducting similar studies in model organisms will open the doors to testing whether these changes are reversible and whether we can turn back the clock when it comes to the aging of our immune systems. The study provides a window on how the cellular orchestra fails with aging and delivers biomarkers that can be used to identify individuals who might be at high risk for age-associated health declines.