Download AGING AND INFLAMMATION Dra. Liseti Solano Rodríguez y M.Sc

AGING AND INFLAMMATION
Dra. Liseti Solano Rodríguez y M.Sc. Junedy Marcano. Instituto de Investigaciones
en Nutrición. Universidad de Carabobo. Venezuela. Correo: [email protected] y
[email protected]
The increase of life expectancy along with decrease in birth rate has originated an
explosive growth of the number and proportion of senior adults. This
epidemiological fact emphasizes the importance of knowing the differences
between aging successfully and not so successfully to be able to make a
contribution to this process in order to lower medical and other inherent social
costs.
One very important fact in aging is the coexistence of alterations of the immune
response, humoral and cellular, known as immunosenescence; which contributes
to increased susceptibility to infections, cancer and other auto immune ailments.
Fortunately these alterations are counterbalanced by body adaptation which occurs
with time and thus allows observation of those adults who manage to live for more
than hundred years.
Aging is a postmaturational event associated to an increased predisposition to
becoming sick and dying, for example a senior adult compared to a person less
than 44 years has forty three times the probability of getting cancer, eighty nine
times to suffer from pneumonia, ninety two times cardiac diseases and hundred
times the possibility of being a victim to ACVs and chronic pulmonary sicknesses.
The susceptibility to and survival from these sicknesses depends greatly on an
optimal functioning of the immune system.
During aging, there is a process of activation of a systemic, chronic, controlled, low
intensity and asymptomatic inflammatory response; changes that are common to
most of aging sicknesses.
The inflammatory process is an extremely complex response to different internal
and ambiental stimuli in which the principal participants are the pro inflammatory
cytokines. Inflammation generates oxygen reactive species which not only causes
oxidative damage but also amplifies the response of cytokines and forms a vicious
cycle generating a chronic pro inflammatory state in which a lesion is created,and
tisular reparation follows and damage accumulates over time, thus promoting aging
and chronic associated ailments such as osteoporosis, sarcopenia, diabetes type
2, Alzheimer, and atherosclerosis.
Various authors suggest that this phenomenon is the consequence of an evolutive
genetic programming in which the pro inflammatory immune response is activated
continuously defending and maintaining life against internal and external
aggressions especially in the first few years. Due to the increase in the span of life,
chronic inflammation occurs and tissue damage appears.
To take into account genetic aspects related to better or worse aging an
immunological risk phenotype (IRP) indicator is used. This indicator uses immune
response parameters and maybe associated to the incapacity to control systemic
inflammation as has been shown in a study of healthy Danish elderly in which it
was observed an association between rate of mortality of all causes with slight
elevation of tumoral necrosis factor (TNF-α) and interleukina-6 (IL-6),
independently from each other and other assessed factors.
To date, the factors responsible for the individual susceptibility are not known but
they are under intense research. It is believed that this susceptibility may be multi
factorial including genetic and ambiental interactions in the control of various
parameters such as cytokine concentration, hormone concentration and the
function of hormonal receptors, anti oxidation defense and reparation of DNA,
function of proteosoma, control of apoptosis, state of histone acetilation, level of
cells such as NK cells, or suppressor cells such as CD4+ CD25+ and positive and
negative molecular co-stimulators over T cells.
It is important that evaluate how much of these changes can be attributed to the
immunogenetic baggage and how much on the natural history of the individual
(effect of elevated anti genetic charges as it happens in chronic infections). Recent
data indicate that some polymorphisms (IL-6-174 C/G) related to the production of
interleukina-6 are predictive to the mortality of elderly people due to infarct of the
myocardium or unstable angina and that there is a significant increase in the antiinflammatory genotype (IL-10 -1082GG/TNF-α-308GG) in people over hundred in
comparison to control groups. This suggests that those persons with a genotype
capable of controlling inflammatory states will age better whereas those with pro
inflammatory genotypes will not age well.
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