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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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Serum markers of apoptosis and tumor stage. Subjects with                                        breast cancer (a, c, e), or prostate cancer (b, d, f) were                                        stratified by stage and the distribution of sFas (a, b), sFasL (c,                                                d) and cytochrome c (e, f)                                        stratified by staging was determined. The solid horzontal bars depict the                                        median values.  For breast cancer, stage I tumor size (T) < 2 cm across                                        and cancer cells have not spread to axillary lymph nodes (N). For stage II,                                        T < 2 cm across and the cancer has spread to the lymph nodes under the                                        arm (N positive) or T is 2 to 5 cm and N is negative. In stage III, T >                                        5 cm or it has spread to other lymph nodes or tissues near the breast.                                        Stage IV is metastatic cancer. The convention for prostate cancer staging                                        was that in stage I, cancer is found in the prostate only. In stage II,                                        cancer is more advanced than in stage I, but has not spread outside the                                        prostate. In stage III, cancer has spread beyond the outer layer of the                                        prostate to nearby tissues. Stage IV is characterized by distant                                        metastasis. Comparison between group median values was performed by Mann                                        Whitney t-test, where * = p < 0.05, ** = p < 0.005, *** = p <                                        0.0001. Numbers in parenthesis indicate number of subjects in each group.
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Figure 6: Serum markers of apoptosis and tumor stage. Subjects with breast cancer (a, c, e), or prostate cancer (b, d, f) were stratified by stage and the distribution of sFas (a, b), sFasL (c, d) and cytochrome c (e, f) stratified by staging was determined. The solid horzontal bars depict the median values. For breast cancer, stage I tumor size (T) < 2 cm across and cancer cells have not spread to axillary lymph nodes (N). For stage II, T < 2 cm across and the cancer has spread to the lymph nodes under the arm (N positive) or T is 2 to 5 cm and N is negative. In stage III, T > 5 cm or it has spread to other lymph nodes or tissues near the breast. Stage IV is metastatic cancer. The convention for prostate cancer staging was that in stage I, cancer is found in the prostate only. In stage II, cancer is more advanced than in stage I, but has not spread outside the prostate. In stage III, cancer has spread beyond the outer layer of the prostate to nearby tissues. Stage IV is characterized by distant metastasis. Comparison between group median values was performed by Mann Whitney t-test, where * = p < 0.05, ** = p < 0.005, *** = p < 0.0001. Numbers in parenthesis indicate number of subjects in each group.

Mentions: The association of cancer stage groupingswith apoptosis markers was investigated for breast and prostate cancer. The breast cancer serum values were segregated by stage where stage I is small localized tumors with no spreading to axillary lymph nodes; stage II disease has larger tumors and potential spread to the lymph nodes; stage III disease has spread to other lymph nodes or tissues near the breast; while stage IV is metastatic cancer. For prostate cancer, stage II cancer is localized within the prostate but palpable, stage III cancer has broken through the covering of the prostate but is still regional, and stage IV cancer has spread to other tissues. When the distribution of sFas, sFasL and cytochrome c were profiled by stage using Tukey box plots, discrete patterns were observed (Figure 6).


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 markers of apoptosis and tumor stage. Subjects with                                        breast cancer (a, c, e), or prostate cancer (b, d, f) were                                        stratified by stage and the distribution of sFas (a, b), sFasL (c,                                                d) and cytochrome c (e, f)                                        stratified by staging was determined. The solid horzontal bars depict the                                        median values.  For breast cancer, stage I tumor size (T) < 2 cm across                                        and cancer cells have not spread to axillary lymph nodes (N). For stage II,                                        T < 2 cm across and the cancer has spread to the lymph nodes under the                                        arm (N positive) or T is 2 to 5 cm and N is negative. In stage III, T >                                        5 cm or it has spread to other lymph nodes or tissues near the breast.                                        Stage IV is metastatic cancer. The convention for prostate cancer staging                                        was that in stage I, cancer is found in the prostate only. In stage II,                                        cancer is more advanced than in stage I, but has not spread outside the                                        prostate. In stage III, cancer has spread beyond the outer layer of the                                        prostate to nearby tissues. Stage IV is characterized by distant                                        metastasis. Comparison between group median values was performed by Mann                                        Whitney t-test, where * = p < 0.05, ** = p < 0.005, *** = p <                                        0.0001. Numbers in parenthesis indicate number of subjects in each group.
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Figure 6: Serum markers of apoptosis and tumor stage. Subjects with breast cancer (a, c, e), or prostate cancer (b, d, f) were stratified by stage and the distribution of sFas (a, b), sFasL (c, d) and cytochrome c (e, f) stratified by staging was determined. The solid horzontal bars depict the median values. For breast cancer, stage I tumor size (T) < 2 cm across and cancer cells have not spread to axillary lymph nodes (N). For stage II, T < 2 cm across and the cancer has spread to the lymph nodes under the arm (N positive) or T is 2 to 5 cm and N is negative. In stage III, T > 5 cm or it has spread to other lymph nodes or tissues near the breast. Stage IV is metastatic cancer. The convention for prostate cancer staging was that in stage I, cancer is found in the prostate only. In stage II, cancer is more advanced than in stage I, but has not spread outside the prostate. In stage III, cancer has spread beyond the outer layer of the prostate to nearby tissues. Stage IV is characterized by distant metastasis. Comparison between group median values was performed by Mann Whitney t-test, where * = p < 0.05, ** = p < 0.005, *** = p < 0.0001. Numbers in parenthesis indicate number of subjects in each group.
Mentions: The association of cancer stage groupingswith apoptosis markers was investigated for breast and prostate cancer. The breast cancer serum values were segregated by stage where stage I is small localized tumors with no spreading to axillary lymph nodes; stage II disease has larger tumors and potential spread to the lymph nodes; stage III disease has spread to other lymph nodes or tissues near the breast; while stage IV is metastatic cancer. For prostate cancer, stage II cancer is localized within the prostate but palpable, stage III cancer has broken through the covering of the prostate but is still regional, and stage IV cancer has spread to other tissues. When the distribution of sFas, sFasL and cytochrome c were profiled by stage using Tukey box plots, discrete patterns were observed (Figure 6).

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