Aging and Infectious Disease-Part VIII
Aging brings on an increased vulnerability to infectious diseases. Central nervous system (CNS) inflammation is associated with various disease processes and neurotrauma. Burns and Goodwin (1997; 5:374-397) state "Aging is associated with decline in multiple areas of immune function, but to date no single mechanism has emerged as being responsible for all the observed changes…. It is being increasingly acknowledged that autoimmune processes play a proinflammatory role in the development of many pathological conditions…." Erschler, in an article in Experimental Gerontology (1998; 23:387-389), suggests that healthy individuals evidence age-related increases in plasma Interleukin-6 levels, a cytokine, which parallel the vulnerability of the central nervous system to injury. Cytokines are intercellular communicating proteins in the immune system and their measurement may provide a sensitive index of inflammatory processes.
Increased serum levels of cytokines are commonly found in infections. In some way activated cells in the aged CNS are primed to be more hypersensitive to infection and at the same time may be too damaged to react normally to invading pathogens. The damage (hypersensitivity) may be the result of free radical involvement with cell membranes.
Free radical damage to immune cell membrane lipids may ultimately impair the ability of immune cells to respond normally to challenge. Cells have to maintain general conditions necessary for life’s chemistry, insulating them from the local environment. The lipid membrane plays this role. It is equipped with pumps and transporters that manage the transportation of molecules in and out of the cell. The cell membrane has surface receptors conducive to chemical reactions.
Normally, oxidation involves the transfer of a pair of electrons from one atom to another. When an unpaired electron escapes, called a free radical, it can cause damage to the molecules in nearby cell membrane. These single electrons, the free radicals, are highly reactive, seeking to capture another electron to complete a pair and in doing so they damage or destroy the function of another molecule. This type of damage could be a major contributing factor to aging and to infectious diseases.
Free radical damage is cumulative, building up with age. The cell membrane lipids, an important role player in nerve function, are oxidized, resulting in impaired cell-to-cell communication and transmission. The immune alert systems are slow to react and the memory to deal with the invading pathogen is impaired. Vulnerability to infections occurs.
This oxidative damage changes the local cellular environment, disrupts cellular signals, changes metabolic pathways, and interferes with immunological functions, with resulting potential for infection. A struggle results, with the body repair system trying to repair the damage. The strength of this repair system is compromised with age and the infection takes over.
Oxidative damage has stimulated interest in antioxidants in preventing the development of infectious diseases. Many healthy individuals are now taking vitamins and other supplements for their "protective effect". Maxwell (1999; 21(4): 253-266), in a review of the literature states: "a number of long term, prospective, randomized, placebo-controlled trials examining the protective effect of antioxidant supplements have now been completed. The results have been generally disappointing and have provided little evidence of efficacy." He also goes on to warn that certain antioxidants, namely betacarotine, might increase the risk of cancer in those individuals who are at high risk for developing this disease.
Another substance that has been implicated in immune system deterioration is DHEA (dehydroepiandrosterone), the most abundant adrenal steroid in young healthy individuals. It is released from the zona reticularus of the adrenals after birth, increasing throughout puberty until maximum serum levels are reached in the third decade of life. Then a slow, steady decline commences of about 2% per year in circulating blood levels. By the time one reaches the eighth decade of life, the levels are at 10-15% of the maximum. This information is arrived at by doing a challenge test (adrenocorticotropic hormone challenge test) on different age groups which indicates that the decline is not the result of a change in the metabolism of DHEA, but instead appears to be affected by a diminished adrenal secretory rate. This is contrasted with the cortisol secretion, which is maintained throughout life. The resulting increase in cortisol/DHEA ratio in the blood may be another culprit partially responsible for the vulnerability that develops during aging. This is further confounded by the loss of receptors for DHEA that arise with aging such that there is an irreversible process rapidly overcoming any attempts to enhance the immune system.
The Center for Disease Control reports that infections are the fifth most common cause of death in the elderly. Most common infections are viral and bacterial. This vulnerability is most likely linked to deterioration in the immune system called immunosenescence. ("Immunosenescence is a complex remodeling of the immune system which may contribute significantly to the morbidity and mortality in the elderly. Immunosenescence due to the accumulation of chromosomal damage and induction of gene products that inhibit cell-cycle progression." See Ginaldi et al 1999; 11:281-286.)
Our protective immunity system shows declines in the formation of affinity antibodies, the generation of long-lasting memory immune responses after vaccination and the expression of delayed-type hypersensitivity reaction to antigens initially encountered earlier in life. Virtually every human being that survives into advanced age expresses this immunodeficiency (immunosenescence) to some extent. The goal now is to map underlying cellular and molecular changes and develop ways to stop the deterioration of the immune system or to beef up this system so that deterioration does not take place.
Antioxidants are not the final answer, but may have a part in immune stimulation, increasing the body's capacity to respond to antigens. DHEA may play a functional role in the maintenance of an immune competent state, reversing some aspects of immunosenescence. In some cases, this may be enough to beef-up the effects of vaccinations. No robust evidence of either role exists in the literature. More research is needed to develop appropriate and effective prevention and intervention protocols to reduce the incidence of infectious disease. This calls for long term prospective studies that are not the "fashionable" studies funded in our society, but are valuable because they can supply answers to the challenge of prevention of infectious diseases and give us insight into reversing the process of aging.
Erschler WB. Interleukin-6: Biomarkers of aging: Immunological events. Exp Gerontol 1998; 23:387-389
Burns EA., and Goodwin JS. Immunodeficiency of Aging. Drug and Aging 1997; 5:374-397. (This review of the physiology of aging contains an excellent bibliography for those readers interested in exploring this topic in depth)
Maxwell, Simon R. J. Antioxidant Vitamin Supplements: Update of their potential benefits and possible risks. Drug Safety. 1999; 21(4): 253-266.
Ginaldi L, DeMartinis M, D’Ostillio A, Marini L, Loreto MF, Quagliono D. Immunological Changes in the Elderly. Aging Clin Exp Res 1999; 11:281-286.
Go Back to Article I of Articles on Aging-Mortality risk factors
The Aging Process-Part II-Gender Difference
The Aging Process-Part III-Cellular Senescence
The Aging Process-Part IV-Biological Aging
Go to Article V of Articles on Aging-Arteriosclerosis
The Aging Process-Part VI-Aging in Males
The Aging Process-Part VII-Aging in Women
Process of Aging-Part IX-DHEA
The Aging Process-Part X-Skin, Skeleton and Brain
The Aging Process:-Part XI-Apotosis and the Elderly
The Aging Process-Part XII-Biomarkers for Aging
The Aging Process- Part XIII- Body Odors
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Harold Rubin, MS, ABD, CRC, Guest Lecturer
September 24, 2000
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