Aging

Aging is a life phase when the risk of inflammatory disease increases; certain protein molecules (called cytokines) can influence lifespan, morbidity, and mortality. During inflammation, mechanisms are challenged to provide adequate defenses against oxidative molecules and an external supply of antioxidants is required. Pro-inflammatory cytokines and oxidant molecules produced from inflammatory responses can be either helpful or harmful, depending on quantity and circumstances of their formation. Slowing cytokine and inflammatory mediator production and maintaining antioxidant defenses are beneficial and depend on adequate nutrient intake, absorption, and utilization. If the body is working correctly, and supplied with adequate nutrition, the nutrients obtained from foodstuffs can influence inflammatory aspects of the immune system and alter cytokine production by limiting the cytokine responsiveness of target tissues. Healthy diets that contain a variety of fruits and vegetables and tea products providing antioxidant nutrients including ascorbic acid, tocopherols, β-carotene, lycopene, and bioflavonoids are recommended.

Aging can initiate chronic inflammation that increases oxidative stress. Nutrients with anti-inflammatory properties, such as vitamin E and n-3 PUFAs, can reduce chronic inflammatory levels and improve tissue and functional loss during aging. Generally, dietary n-6 PUFA greatly exceeds dietary n-3 PUFA intake. Arachidonic acid (an n-6 PUFA) stimulates inflammatory mediator production including cytokine fabrication and other immune system stability. Fish oil and oily fish are good sources of long chain n-3 PUFA. Consumption of n-3 PUFAs reduces arachidonic acid available for inflammatory mediator production; thus, acting as an arachidonic acid antagonist and affecting cytokine production. n-3 PUFA may be used therapeutically for acute and chronic inflammation and for other diseases involving inappropriately activated immune responses. n-3 PUFAs, glutamine, arginine, sulfur amino acids, nucleotides, and N-acetyl-cysteine (NAC) are important components of immunonutrient mixes which have properties to suppress inflammation. n-3 PUFAs can directly control the inflammatory process, while glutamine and NAC have indirect effects on the antioxidant condition.  Omega-3 FAs have been used as an adjunctive therapy for temporo-mandibular joint dysfunction, and systemically to decrease inflammation.

Polyamine synthesis is a response to infection and during tissue repair and recycling. Recycling is a key feature of polyamine metabolism, requiring ornithine, arginine, and adequate tissue S-adenosyl methionine (SAMe), during periods of rapid cell growth. During an immune/inflammatory response, the combination of enhanced utilization of cysteine for glutathione synthesis and cell replication may lead to cellular SAMe depletion. The addition of these amino acids and polyamines to the diet can help improve amino acid balance and may improve antibacterial defenses.

Cytokines enhance oxidant production and antioxidant defenses. Antioxidant defenses work together when a component is compromised; however the nature and extent of the defenses are prejudiced by dietary intake of sulfur amino acids, glutathione synthesis, and vitamins E and C. Vitamins E and C and glutathione are closely connected in antioxidant protection. Animal studies show that reaction to inflammatory stimuli are prejudiced by dietary intake of copper, zinc, selenium, N-acetylcysteine (NAC), cysteine, methionine, taurine, and vitamin E. Pro-inflammatory cytokines also mediate extensive alterations in protein metabolism. Amino acids released from peripheral tissues during inflammatory processes can act as substrates for acute phase proteins and immunoglobulin synthesis and, with polyamines, replication of immune cells. Demands for specific amino acids can exceed the body’s stores. Sulfur amino acid insufficiency compromises glutathione synthesis resulting in compromised antioxidant defenses. Increased nitrogen excretion also occurs during the immune response with phenylalanine, tyrosine, tryptophan, serine, and cysteine being released in amounts closest to their requirements. Accordingly, sulfur amino acids and metabolically related amino acids may be required in increased amounts.

Irregular or excessive manufacture of cytokines and oxidant molecules can lead to inflammatory diseases and inflammation in the blood, triggering an increased possibility of cytokine-induced illness and death. Multifaceted systems manage cytokine manufacture and oxidant events: hormones of the hypothalamo-pituitary-adrenal axis, acute phase proteins, and endogenous inhibitors of IL-1 and TNF. Others consist of endogenously synthesized antioxidants, such as glutathione and dietary antioxidants (e.g., tocopherols, ascorbates, and catechins). Genetic factors can also influence the effectiveness of immunonutrients, such as antioxidants and n-3 PUFA.

Certain macro- and micronutrients also influence antioxidant enzyme activities and total body health. Stimulation of the immune system increases antioxidant enzyme activity that can detoxify oxidative molecules.  Whey protein is a powerful antioxidant found in milk. Its action is due to its high concentration of the amino acid cysteine, a component of glutathione (a natural antioxidant of the body).  Whey protein also contains numerous important biological components that can improve immune system function. Approximately 15% of whey proteins are immunoglobulins; antibodies that bestow immunity. Protein deficiencies weaken the immune system by reducing antibody formation and cellular activities that ingest bacteria, the body’s ability to manufacture immunoglobulins, and other non-specific resistance factors. Lactoferrin, a major component of whey protein, acts as a systemic antioxidant. Lactoferrin can reduce adhesion of several oral bacteria; stop growth of certain periodontitis-causing bacteria; and kill certain periodontitis- and caries-causing bacteria. Lactoferrin is also found ubiquitously and abundantly in human endocrine secretions, and lactoferrin in neutrophils has been used to monitor inflammatory responses. Lactoferrin, when applied locally, can resolve oral lesions. Lysine is also used treat aphthous and herpes ulcers, and  systemically as an essential amino acid.

Antioxidants are dietary substances found in foods that counteract the damaging effects of reactive species on cells and may protect against chronic disease.  The antioxidant nutrients that impact the immune response include vitamin A, vitamin C, vitamin E, zinc, copper, iron, and selenium.  Selenium is an essential component of antioxidant enzymes.  These enzymes reduce hydrogen peroxides and other intermediates that potentially damage biomolecules.

Increased risk of malabsorption of β-carotene and fat soluble vitamins (A, D, E, K) are involved in bone mineralization and antioxidant function. Medications increase risk for calcium, magnesium, iron, and zinc deficiency, which can lead to anemia and immune function abnormalities. Selenium depletion can lead to lower immunity and reduced antioxidant protection. Tryptophan and tyrosine deficiencies can cause mental depression.

Inverse relationships between body levels of DHEA and several diseases,  including diabetes and CVD, have been reported. Animal studies showed that DHEA improved immune function and memory and prevented atherosclerosis, cancer, diabetes, and obesity. DHEA is a prohormone. Its production peaks about age 25 and then declines approximately 2% yearly until the end of life. DHEA sulfate (DHEAS) is an inactive metabolite of DHEA; however DHEA and DHEAS can both be converted into numerous active metabolites, as originators of about half of male androgens, 75% of active pre-menopausal estrogens and all active estrogens post-menopausal. Proper hormonal and endocrine functions are required for effective nutrient assimilation and functioning.

As free radical scavengers, flavonoids inhibit lipid peroxidation, promote vascular relaxation, and help prevent atherosclerosis. Oxidized LDLs are highly atherogenic and stimulate macrophage cholesterol accumulation and foam cell formation, which are cytotoxic to cells of the arterial wall stimulating inflammatory and thrombotic processes. Dietary flavonoid supplementation in combination with vitamin C significantly reduced neutral and polar liver lipids in rats fed a high coconut oil diet. Combined antioxidants, such as vitamin E, beta-carotene, and polyphenolic flavonoids have an additive effect in  reducing LDL oxidation.

Malnutrition is characterized by marked tissue depletion of the key antioxidant nutrients, including gamma-glutamyl-cysteinyl-glycine (GSH), and impaired acute-phase protein response to infections. Acute-phase protein response plays a key role in promoting healing, and its deficit in malnutrition is due to impairment of cytokines production and cellular action. Other features of malnutrition include immune dysfunction, histaminemia, hormonal imbalance with increased blood and saliva levels of free cortisol, and defective mucosal integrity.