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Apoptosis--programmed cell death: a role in the aging process?
1Istituto di Patologia Generale, Università degli Studi di Modena, Italy.
Abstract:
Cells continuously exposed to genotoxic agents, such as oxygen free radicals (OFRs), deeply involved in the aging process use a variety of cellular defense mechanisms. These defense mechanisms include DNA repair enzymes, antioxidants, poly(ADP-ribosyl)polymerase (pADPRP), and stress proteins and they constitute an integrated network. An age-related failure of the efficiency of this network can affect cell proliferation and cell death, two phenomena tightly linked and regulated. Recent data from our laboratory on the role of DNA damage and pADPRP activation and on the type of cell death induced by OFRs in human lymphocytes are reviewed. In vitro and in vivo data on possible strategies to reduce oxidative stress in lymphocytes from normal and Down syndrome subjects, by using natural compounds and trace elements, are presented. They indicate that nicotinamide and L-carnitine protect human cells from OFR-induced damage and suggest that they are possible candidates as antiaging substances.
Insights
Cellular defense networks decline with age, impacting cell death and proliferation. Nicotinamide and L-carnitine show potential as anti-aging substances by protecting cells from oxygen free radical damage.
Area of Science:
- Cellular and Molecular Biology
- Aging Research
- Genotoxic Stress Response
Background:
- Cells possess integrated defense networks involving DNA repair, antioxidants, poly(ADP-ribosyl)polymerase (pADPRP), and stress proteins to combat genotoxic agents like oxygen free radicals (OFRs).
- Age-related decline in the efficiency of these cellular defense mechanisms can disrupt cell proliferation and cell death regulation.
- Oxygen free radicals (OFRs) are implicated in the aging process and cellular damage.
Purpose of the Study:
- To review the role of DNA damage and pADPRP activation in human lymphocytes exposed to OFRs.
- To investigate the type of cell death induced by OFRs in human lymphocytes.
- To present in vitro and in vivo data on strategies to mitigate oxidative stress in lymphocytes from normal and Down syndrome subjects.
Main Methods:
- Review of laboratory data concerning DNA damage, pADPRP activation, and OFR-induced cell death in human lymphocytes.
- In vitro and in vivo experiments using natural compounds and trace elements to reduce oxidative stress.
- Assessment of protective effects of nicotinamide and L-carnitine on human cells against OFR-induced damage.
Main Results:
- Data reviewed highlight the connection between DNA damage, pADPRP activation, and OFR-induced cell death pathways in lymphocytes.
- Nicotinamide and L-carnitine demonstrated protective effects against OFR-induced cellular damage in human lymphocytes.
- The study explored strategies for reducing oxidative stress in lymphocytes from both normal and Down syndrome individuals.
Conclusions:
- Nicotinamide and L-carnitine are effective in protecting human cells from oxygen free radical-induced damage.
- These compounds show promise as potential anti-aging substances due to their protective effects on cellular defense mechanisms.
- Targeting oxidative stress in lymphocytes may offer therapeutic strategies for age-related decline and associated conditions.