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Serum markers of apoptosis decrease with age and cancer stage.

Kavathia N, Jain A, Walston J, Beamer BA, Fedarko NS - Aging (Albany NY) (2009)

Bottom Line: The physical manifestations of aging reflect a loss of homeostasis that effects molecular, cellular and organ system functional capacity.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA.

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.

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Related in: MedlinePlus

Serum total cytochrome c levels. The levels of                                        total cytochrome c in 204 normal                                        subjects were determined as depicted in Figure 3. The frequency                                        distribution of the values across the subjects was analyzed (a). The                                        levels of total cytochrome c in all                                        subjects by gender was plotted (b). The sample population was                                        segregated by gender and the levels of serum cytochrome                                        c as a function of donor age for female (c) and male (d)                                        subjects were plotted.
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Figure 4: Serum total cytochrome c levels. The levels of total cytochrome c in 204 normal subjects were determined as depicted in Figure 3. The frequency distribution of the values across the subjects was analyzed (a). The levels of total cytochrome c in all subjects by gender was plotted (b). The sample population was segregated by gender and the levels of serum cytochrome c as a function of donor age for female (c) and male (d) subjects were plotted.

Mentions: The mean value for serum levels of total cytochrome c was 0.71 ± 0.42 μg/ml. The frequency distribution of serum values was analyzed by histogram and a nonparametric distribution was evident (Figure 4a). When the results were stratified by gender, the difference in mean (and median) values by gender were not significant (Figure 4b and Table 1). Plotting total cytochrome c levels versus the age of the subject revealed that both genders exhibited an age-dependent decrease in total cytochrome c, though the slopes appeared to be different (Figure 4c and d).


Serum markers of apoptosis decrease with age and cancer stage.

Kavathia N, Jain A, Walston J, Beamer BA, Fedarko NS - Aging (Albany NY) (2009)

Serum total cytochrome c levels. The levels of                                        total cytochrome c in 204 normal                                        subjects were determined as depicted in Figure 3. The frequency                                        distribution of the values across the subjects was analyzed (a). The                                        levels of total cytochrome c in all                                        subjects by gender was plotted (b). The sample population was                                        segregated by gender and the levels of serum cytochrome                                        c as a function of donor age for female (c) and male (d)                                        subjects were plotted.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806040&req=5

Figure 4: Serum total cytochrome c levels. The levels of total cytochrome c in 204 normal subjects were determined as depicted in Figure 3. The frequency distribution of the values across the subjects was analyzed (a). The levels of total cytochrome c in all subjects by gender was plotted (b). The sample population was segregated by gender and the levels of serum cytochrome c as a function of donor age for female (c) and male (d) subjects were plotted.
Mentions: The mean value for serum levels of total cytochrome c was 0.71 ± 0.42 μg/ml. The frequency distribution of serum values was analyzed by histogram and a nonparametric distribution was evident (Figure 4a). When the results were stratified by gender, the difference in mean (and median) values by gender were not significant (Figure 4b and Table 1). Plotting total cytochrome c levels versus the age of the subject revealed that both genders exhibited an age-dependent decrease in total cytochrome c, though the slopes appeared to be different (Figure 4c and d).

Bottom Line: The physical manifestations of aging reflect a loss of homeostasis that effects molecular, cellular and organ system functional capacity.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA.

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.

Show MeSH
Related in: MedlinePlus