Mechanisms of Inflammation in Aging – The redox stress hypothesis

We have just introduced the effects of inflammation in aging in our pervious article and now we want to progress with the discussion focusing on the mechanisms of inflammation in aging. If you are joining us for the first time in this life changing site, I would recommend that you get to the introduction for a better flow of information on this worthy topic. Numerous complex inter-related mechanisms contribute to age-related inflammation. The redox stress hypothesis of aging for example is based on age-related changes in cellular redox balance supplemented by age-related deregulation of the immune system. However other processes like endocrino-senescence and declining levels of sex hormones also likely contribute to high inflammation in older age. In addition, a number of diseases, especially age-related diseases such as atherosclerosis and dementia, have strong inflammatory components. Meanwhile in view of the experts at AWAREmed Health and Wellness Resource Center under Doctor Akoury’s care, the following are some of the components that are likely to affect your skin into premature aging.

• Redox stress
• Mitochondrial damage
• Immunosenescence
• Endocrino-senescence
• Epigenetic modifications and
• Age-related diseases

With the help of experienced experts at this facility founded by doctor Akoury, we will make certain emphasis about each of the above mechanisms of inflammation in aging as follows.

Mechanisms of Inflammation in Aging – The Redox stress

Endogenous reactive oxygen species (ROS) are hypothesized which play a key role in molecular, cellular, and structural damage of your skin over time. Under normal physiological conditions, reactive oxygen species like hydrogen peroxide (H₂O₂) have vital roles in signal transduction cascades and function to reversibly oxidize or reduce protein cysteine thiol groups as molecular on/off switches. However, age-associated increases in reactive oxygen species may lead to over-oxidation and irreversible changes in protein structure and function. The biological process to remove these accumulated damaged proteins stimulates inflammatory responses leading to a chronic inflammatory state.

Mechanisms of Inflammation in Aging – The Mitochondrial damage

Mitochondria, the primary sites for chemical energy (ATP) production, are essential for normal cell function and maintenance of redox homeostasis as well as regulating programmed cell death. Mitochondria are the main source for reactive oxygen species therefore; they are key components in redox stress. The mitochondrial free radical theory of aging is based on oxidative damage to mitochondrial DNA (mtDNA) due to overproduction of reactive oxygen species. This damage results in dysregulation of cell and organ function leading to the overall system decline recognized as aging. mtDNA alterations have been reported to accumulate with age; the ensuing loss of energy production likely underlies sarcopenia. Other tissues affected by age-related mtDNA alterations include ovary, testis, and adrenal organs with noted loss of function with age. In addition, apoptosis, or programmed cell death, is a highly regulated process that leads to cell death without stimulation of the inflammation response and damage to surrounding tissue. With age, mismanagement of apoptosis due to mitochondrial dysfunction results in increased inflammation and tissue injury.

Mechanisms of Inflammation in Aging – Immunosenescence

Oxidative stress and energy dysregulation are also hypothesized to play a key role in immunosenescence, the gradual decline of the immune system with age. Immunosenescence results from the accumulation of molecular and cellular defects due to oxidative damage and thymic involution the age-related reduction in thymus size and activity, and hyper stimulation of both the innate and adaptive immune systems. The ultimate result of these processes is increased exposure to diseases and increased morbidity and mortality due to infections and other age-associated diseases.

Thymic involution results in significantly reduced levels of naive T cells at older ages. While the adaptive immune response to previously seen antigens dependent on memory T cells remains functional, although in a reduced capacity, the ability to respond to new infectious agents, requiring naive T cells, is severely impaired. Poor immune function combined with continued exposure to antigens, results in chronic activation of macrophages and other pro-inflammatory cells and contributes to chronic low level inflammation common in older age. In addition, senescent cells demonstrate significant increases in production and secretion of many pro-inflammatory cytokines. Chronic inflammation, therefore, not only results from, but also drives immunosenescence.

Mechanisms of Inflammation in Aging – Endocrino-senescence

In addition to immunosenescence, the endocrine system also experiences age-related declines in function (endocrinosenescence) most notably affecting sex steroid production. Levels of growth hormone and dehydroepiandrosterone (DHEA) and its primary circulating form dehydroepiandrosterone sulfate (DHEAS) decrease with age as well. However, cortisol production is increased due to over-stimulation of the hypothalamic-pituitary-adrenal (HPA) axis.

Chronic over-stimulation of the hypothalamic-pituitary-adrenal axis leads to immune dysregulation and contributes to immunosenescence. Decreased levels of DHEA and growth hormone also likely play a role in immunosenescence. Both DHEA and growth hormone enhance the proliferation and activity of cellular mediators of immunity and DHEA reduces inflammatory cytokine production. Reduction in levels of these hormones and increasing levels of cortisol with age would therefore lead to increased.

Sex hormones also modulate the production of inflammatory cytokines. Studies indicate that interleukin-6 gene transcription and secretion are inhibited by both estrogen and androgen. Many studies show an increase in interleukin-6 and other pro-inflammatory cytokines in women subsequent to menopause. Similar inverse relationships have been reported for testosterone levels and inflammatory markers in older men. As levels of these steroid hormones decrease with age, levels of inflammatory cytokines are increased contributing to chronic inflammation, cellular senescence, and other age-related diseases.

Mechanisms of Inflammation in Aging – Epigenetic modifications

Epigenetic modifications are modifications to phenotypes or gene expression resulting from changes other than changes in the underlying DNA sequence. These changes may be retained by the cell throughout its lifespan and, for germ line cells, may be passed to future generations. DNA methylation is one of the most well characterized epigenetic changes.

DNA methylation is essential for normal development and survival. During aging, however, the DNA methylation pattern can change resulting in a global decrease in methylation with hyper methylation of some promoter regions, most notably promoters of several tumor repressor genes. Histone modifications lead to both gene activation and suppression. Histone modifications and changes in DNA methylation near telomeric regions correlate with telomere attrition and cellular senescence. In addition, these epigenetic changes are associated not only with activation of inflammatory genes, but also with cancer, dementia, atherosclerosis, and a number of other diseases.

Finally this article is very fertile with strong medical terms which may not sound clear to the ordinary man’s understanding. While appreciating the need for more clear view of the effects of mechanisms of inflammation in aging, the writings still had to be the way they are. However in a one on one with doctor Akoury in her office, you will be able to get clarity in all of your concerns. Remember that our target is to deliver beauty to you in the most professional way. Therefore on your part, what you need to do is to schedule for an appointment with the experts at AWAREmed Health and Wellness Resource Center under Doctor Akoury’s care and all your beauty concerns will be professionally addressed.

Mechanisms of Inflammation in Aging – The redox stress hypothesis