Research Paper|Volume 1, Issue 7|pp 652—663

Serum markers of apoptosis decrease with age and cancer stage

Nilay Kavathia^1,², Alka Jain¹, Jeremy Walston¹, Brock A. Beamer^1,³, Neal S. Fedarko¹

¹Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA
²Current address: Thomas Jefferson University, Philadelphia, PA 19107, USA
³Current address: University of Maryland, School of Medicine, Baltimore, MD 21201, USA

Received: June 11, 2009Accepted: July 12, 2009Published: July 14, 2009

Copyright: © 2009 Kavathia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The physical manifestations of aging reflect a loss of homeostasis that effects molecular, cellular and organ system functional capacity. As a sentinel homeostatic pathway, changes in apoptosis can have pathophysiological consequences in both aging and disease. To assess baseline global apoptosis balance, sera from 204 clinically normal subjects had levels of sFas (inhibitor of apoptosis), sFasL (stimulator of apoptosis), and total cytochrome c (released from cells during apoptosis) measured. Serum levels of sFas were significantly higher while sFasL and cytochrome c levels were lower in men compared to women. With increasing age there was a decrease in apoptotic markers (cytochrome c) and pro-apoptotic factors (sFasL) and an increase in anti-apoptotic factors (sFas) in circulation. The observed gender differences are consistent with the known differences between genders in mortality and morbidity. In a separate cohort, subjects with either breast (n = 66) or prostate cancer (n = 38) exhibited significantly elevated sFas with reduced sFasL and total cytochrome c regardless of age. These markers correlated with disease severity consistent with tumor subversion of apoptosis. The shift toward less global apoptosis with increasing age in normal subjects is consistent with increased incidence of diseases whose pathophysiology involves apoptosis dysregulation.