Research Report 2010 2011 - Helmholtz-Zentrum für ...

RESEARCH REVIEWS | The Aging of the Immune System: Challenges and Perspectives
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Fig 2. Loss of naive cytotoxic T-lymphocytes in aged
individuals (adapted from Cicin-sain et al. PNAS 2007). The
population of naive lymphocytes, characterized by low CD95
and high CD28 expression, is typically abundant in young
adult rhesus monkeys, but severely diminished in old ones.
This results in relative increases of memory subsets. Graphic: HZI
Fig. 1. The male (blue histogrammes) or female (red histogrammes)
general population has been traditionally
distributed across age categories to form a pyramid, where
the most numerous individuals were present in the youngest
age cohorts. In Germany, the demographic changes resulted
in an altered, mushroom shaped, distribution. If current
trends persist, in 25 years the population between 65 and 75
years of age will be the most frequent one. Graphic: HZI
On the other hand, there is a clear consensus that aging
adversely affects the adaptive branch of the immune system,
and in particular the response to emerging infections
occurring in individuals that have reached an advanced age
(Nikolich-Zugich and Rudd, 2010). In contrast, the memory
responses to pathogens and vaccines encountered earlier in
life are maintained even in very advanced age (Ammana et
al., 2007). Consequently, clonally diverse naïve lymphocytes
are more profoundly affected by aging than clonally restricted
memory subsets. Therefore, the loss of clonal diversity in
the lymphocyte pool is a prominent change associated with
immunosenescence.
The causes of immunosenescence are multiple and not entirely
understood. Among the well characterized contributors
to immune aging are the thymic involution and the consequent
loss of newly generated naïve T cells (Figure 2) as
well as metabolic stress, in particular oxidative stress (Altmeyer
and Hottiger, 2009). It remains less clear if inflammatory
conditions contribute to immune aging or are merely
a consequence of immunosenescence. Similarly, the role
of chronically persisting infections in immunosenescence
is not entirely understood (Virgin et al. 2009) and it is not
clear if persistent infections contribute to immune aging or
if immunosenescence results in chronic infections. These
questions can be answered by experimental modelling of
the immune processes in aging animals.
Immunosenescence has multiple clinical consequences.
The elderly show a significant increase in the susceptibility
to infections that are controlled by naïve lymphocyte
populations, such as emerging influenza strains, West Nile
Virus infections or pneumococcal infections. This problem
is complicated by the inability of naïve cell populations to
generate protective immunity upon vaccination in elderly
individuals. On the other hand, the elderly are also more
vulnerable to a variety of other conditions, particularly
chronic inflammatory conditions including arthritis,
inflammatory bowel disorders, atherosclerosis or conditions
with a strong inflammatory component like diabetes or
Alzheimer disease.
Our understanding of the cellular and molecular changes
that underlie the decline in immune function with age has
increased significantly in recent years, and clinical trials to
evaluate methods by which to augment immunity in elderly
individuals are now underway.