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Modulation of gene expression in autoimmune disease and aging by food restriction and dietary lipids
G Fernandes1, J Venkatraman, A Khare
1Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.
Abstract:
Several recent observations carried out by many investigators have offered some clues in understanding the mechanism of how food restriction (FR) acts in the prolongation of life-span, but the precise mechanisms involved in modulating the immune system have not been clearly understood. Our own ongoing studies indicate that FR may act at the molecular level and may extend the life-span by modulating functional activities of several genes in various target tissues. For instance, while cytochrome P-450 IIB1 and IIB2 expression is known to decline with age in ad libitum-fed rats, FR prevented the loss of (drug-inducible) P-450 enzymes in liver tissues. In addition, both alpha 2u-globulin and senescence marker protein 2 expressions, which are regulated by hormones, were also modulated during aging by FR in Fischer 344 male rats. In short-lived autoimmune-prone mice, both FR and omega-3 (n-3) fatty acids diet lowered the severity of autoimmune disease both in lupus-prone (NZB x NZW)F1 mice and in mice prone to develop lymphoproliferative and renal diseases, whereas saturated (n-9) and polyunsaturated (n-6) dietary lipids not only exacerbated autoimmune disease, but also significantly enhanced expression of several oncogenes in lymphoid tissues. FR and omega-3 fatty acids decreased the expression of certain oncogenes. Both FR and omega-3 fatty acids may modulate the aging and autoimmune disease processes by not only altering the fatty acid composition, membrane fluidity, and signal transduction, but also by modulating the lymphokine hormone receptors and their functions and thereby modulating expression of several genes in various tissues during the aging process.
Insights
Food restriction (FR) and omega-3 fatty acids extend lifespan by modulating gene expression and immune responses. These interventions impact molecular pathways, reduce autoimmune disease severity, and decrease oncogene expression in aging tissues.
Area of Science:
- Gerontology
- Immunology
- Molecular Biology
Background:
- Food restriction (FR) is known to prolong lifespan, but its precise mechanisms, especially immune system modulation, remain unclear.
- Aging is associated with declining cytochrome P-450 enzyme expression and altered gene regulation, impacting tissue function.
- Autoimmune diseases and oncogene expression are influenced by dietary lipids and aging processes.
Purpose of the Study:
- To investigate the molecular mechanisms by which food restriction (FR) extends lifespan.
- To elucidate how FR and dietary fatty acids modulate immune system function and age-related gene expression.
- To determine the effects of FR and omega-3 fatty acids on autoimmune disease severity and oncogene expression.
Main Methods:
- Examined the effects of FR on cytochrome P-450 IIB1/IIB2 and alpha 2u-globulin expression in aging Fischer 344 male rats.
- Assessed the impact of FR and omega-3 (n-3) fatty acids on autoimmune disease severity in lupus-prone (NZB x NZW)F1 mice and other prone mouse models.
- Analyzed the influence of dietary lipids (n-3, n-9, n-6) on oncogene expression in lymphoid tissues.
Main Results:
- FR prevented age-related decline in drug-inducible P-450 enzymes in liver tissues.
- FR and n-3 fatty acids reduced autoimmune disease severity and oncogene expression in susceptible mice.
- Saturated (n-9) and polyunsaturated (n-6) lipids exacerbated autoimmune disease and increased oncogene expression.
Conclusions:
- FR and omega-3 fatty acids extend lifespan and modulate aging processes at the molecular level by altering gene expression.
- These dietary interventions impact immune function, reduce autoimmune disease, and decrease oncogene expression, potentially through altered membrane properties and signaling pathways.
- FR and omega-3 fatty acids offer a potential therapeutic strategy for age-related diseases and immune dysregulation.