By Michelle S. Cotroneo, Ph.D., Scientific Advisor

Approximately 1 out of every 6 men will be diagnosed with prostate cancer. Prostate cancer is the most common non-cutaneous malignancy and is second only to lung cancer in deaths due to cancer in American men. Prostate cancer is a disease of aging, with a median age of 79 years (1). Latent prostate cancer, which causes no clinical manifestations, is often found at autopsy by microscopic examination of prostatic tissue. Analysis of autopsy data showed that 15 to 30% of men over the age of 50 had latent prostate cancer, with the incidence increasing to 60-70% by the age of 80 (2,3). In a society where life expectancy has increased, it is important to determine how aging is related to prostate cancer risk.

An important research approach begins at the cellular level. Such studies characterize the interaction between cancerous cells and those that surround them. Senescent cells are those that have lost the ability to divide, and are considered to be “aged”. It is hypothesized that senescent cells may create a permissive or growth-stimulatory environment for cancerous cells. Experimental data have shown that cells immediately surrounding a prostate carcinoma (stromal cells) can cause tumor progression (4). Cellular interactions are mediated by various proteins, including growth factors and enzymes.

In addition to studying interaction between cells, characterizing the relationship between aging and disease often involves examining signaling pathways that occur within cells. One signaling pathway with an important role in both aging and prostate cancer is mediated by the cellular enzyme, mTOR (mammalian target of rapamycin), which functions in cellular growth and metabolism. mTOR signaling is frequently increased in prostate and other cancers. Experimental evidence shows that inhibition of this pathway in living organisms prolongs lifespan, a result that is also achieved with calorie restriction (5); therefore, this pathway may play a central role in age-related cancer.

Other theories about how advancing age is a risk factor for certain diseases focus on the role of accumulating damage to DNA. Recent advances in technology are helping researchers conduct large scale genetic association studies to determine gene-disease relationships. Investigators test human DNA samples for the presence of aberrant chromosomal regions, genes, or single nucleotides. Statistical testing is used to determine if a particular variant occurs with higher frequency in samples derived from diseased individuals, compared to those from persons not having the disease. Interestingly, a review of the recent data from such studies has revealed that there are several prostate cancer variants which serve functions in aging-related cellular pathways (6).

Despite the varying approaches of researchers studying age-related diseases, they share a common goal: to develop strategies to treat or prevent disease.

References

1. Yancik R. Cancer J 2005; 11:437-441.

2. Pienta KJ, Esper PS. Ann Intern Med 1993; 118:793-803.

3. Franks LM, Durh MB. Lancet 1956; 17:1037-1039.

4. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. Cancer Res 1999; 59:5002-5011.

5. Blagosklonny MV. Cancer Biology & Therapy 2008; 7:1520-1524.

6. Cluett C, Melzer D. Mechanisms of Ageing and Development 2009; 130: 553–563.