Aging is the process during which structural and functional changes accumulate in an organism as a result of the passage of time. The changes manifest as a decline from the organism’s peak fertility and physiological functions until death. It is the inevitable time-dependent decline in physiological organ function and is a major risk factor for cancer development.
According to the US National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) Database, 43% of men and 38% of women will develop invasive cancer over a lifetime. Among these, 23% of men and 19 % of women will die from cancer.
Now, a new study conducted by researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine enlightens the factors associated with cellular aging and cancer risk.
The study suggests that epigenetic changes in hematopoietic (blood-forming) stem cells, as people age, may contribute to acute myeloid leukemia (AML) and possibly other blood cancers.
Sylvester’s Maria Figueroa, M.D., associate professor of human genetics said, “If you think of all the genetic material as hardware, the epigenome is the software of the cell, responsible for determining the cell’s behavior. We hypothesized that, with age, this epigenetic program is getting corrupted, which turned out to indeed be the case. As we age, there are significant changes, resulting in the epigenetic reprogramming of important regulatory components of the genome. Once this happens, they can’t do their jobs as well as they could when they were young.”
During the study, scientists collected hemopoietic stem cells (HSCs) from 41 people between 18 and 30, and 55 people between 65 and 75, none of whom had cancer. Determining epigenetic markers and gene expression levels in 59 donors, scientists found epigenetic changes as HSCs age, that thus increase gene expression. In particular, these variations altered several genes that are essential for the normal functioning and differentiation of HSCs.
Dr. Figueroa noted, “Most notably, there’s a core set of changes that were reproducibly found among all individuals. When those epigenetic changes affect certain genes, they put us at risk for malignant transformation. Many of these epigenetic changes affected regulatory regions of several transcription factors — proteins that control the expression of other genes. One of these, called KLF6, is important for blood formation and can be altered in AML.”
In addition, many epigenetic and expression changes were detected as HSCs aged were similar to those seen in cancer cells. Though ominous, that does not mean they will become cancerous.
Dr. Figueroa notes that cells don’t exist in isolation. They live in a microenvironment — in this case, bone marrow. The health of that environment, as well as external factors such as environmental exposures or co-existence of other stressors, may contribute to their ultimate fate.
Dr. Figueroa said, “Not everyone who ages gets cancer and not everyone who has these epigenetic changes, or even gene mutations, gets cancer, either. We hope this study will lead to further research into age-related changes to identify which of these changes and which co-existing factors are really critical to put us at risk for cancer, and if there is anything we can do to intervene and stop those changes.”
Scientists reported their findings on May 13 in the journal Cancer Discovery.