The study, published November 30 in PLoS Genetics, uses a newly available database called AGEMAP to document the process of aging in mice at the molecular level. The work describes how aging affects different tissues in mice, and ultimately could help explain why lifespan is limited to just two years in mice.
As an organism ages, most tissues change their structure (for example, muscle tissues become weaker and have slow twitch rather than fast twitch fibers), and all tissues are subject to cellular damage that accumulates with age. Both changes in tissues and cellular damage lead to changes in gene expression, and thus probing which genes change expression in old age can lead to insights about the process of aging itself.
Previous studies have studied gene expression changes during aging in just one tissue. The new work stands out because it is much larger and more complete, including aging data for 16 different tissues and containing over 5.5 million expression measurements.
One noteworthy result is that some tissues (such as the thymus, eyes and lung) show large changes in which genes are active in old age whereas other tissues (such as liver and cerebrum) show little or none, suggesting that different tissues may degenerate to different degrees in old mice.
Another insight is that there are three distinct patterns of aging, and that tissues can be grouped according to which aging pathway they take. This result indicates that there are three different clocks for aging that may or may not change synchronously, and that an old animal may be a mixture of tissues affected by each of the different aging clocks.
Finally, the report compares aging in mice to aging in humans. Several aging pathways were found to be the same, and these could be interesting because they are relevant to human aging and can also be scientifically studied in mice.
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According to Fowke, obese men are also more likely to present with prostate cancer at an advanced stage. Most prostate cancer is diagnosed in response to a PSA test, and a high body mass index (BMI) often corresponds with lower blood PSA levels.
Diabetes and metabolic disturbances associated with insulin regulation are more common among African-Americans compared to Caucasians, and metabolic disorders associated with obesity and diabetes may lower PSA levels and may cause a delay in referring a patient for a biopsy, Fowke said. This may be in part why we often don't detect prostate cancer in African-American men until it is already fairly advanced.
Given the increasing rates of obesity and diabetes among African-Americans, Fowke and his colleagues sought a better understanding of the relationship between race, metabolic disorders and PSA levels used to detect early-stage prostate cancer.
The researchers examined participants in the Southern Community Cohort Study, a National Cancer Institute-funded initiative that monitors the health of 90,000 men and women between the ages of 40 and 79 throughout the southern United States. The researchers randomly selected 121 African-American men and 121 Caucasian men; each group had the same proportion of obese and overweight men, as determined by their BMI. Study participants had no prior diagnosis of cancer or diabetes.
From each participant's blood sample, the researchers compared PSA levels with the amounts of HbA1c, C-peptide, leptin and adiponectin “ naturally occurring blood-borne molecules that have a biological role in metabolism, insulin activity, or the function of fat cells. Among African-Americans, PSA levels were 50 percent lower among men with higher levels of C-peptide, a biomarker that reliably indicates an increase in insulin. This association was especially prevalent among obese African-American men, Fowke says. PSA levels also declined somewhat among obese Caucasian men with high C-peptide levels, but this relationship was not as strong as it was in the African-American group.
The researchers saw a similar pattern in Caucasian men regarding the diabetes biomarker HbA1c, where PSA levels were 50 percent lower among men with higher levels of HbA1c. PSA levels were not associated with HbA1c in the African-American group, perhaps suggesting that there may be differences between Caucasian and African-American men in the way PSA responds to obesity.
There are a number of complex components related to obesity and insulin activity, and we are seeing that metabolic disturbances can have an effect on PSA levels, Fowke said. It doesn't invalidate PSA screenings, but it does demonstrate that we need research to better understand how obesity and diabetes may be affecting our ability to detect early-stage prostate cancer among African-American men at high-risk for advanced prostate cancer.
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