Aging and Systemic Lupus Erythematosus - Immunosenescence and Beyond
Lucas Laurens van den Hoogen,
Gary Patrick Sims,
Joel Adrianus Gijsbert van Roon,
Ruth Dorothea Elisabeth Fritsch-Stork.
The lifespan of humans has increased drastically over the last decades; considerable effort
has been applied to delineate the mechanisms behind aging in order to find strategies for longevity. As
the benefits of the gained knowledge might extend to diseases, where accelerated aging is suspected,
the role of aging in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) is of particular
interest. In this review the immunological similarities of SLE and aging are analyzed on three
levels: the clinical, the cellular and the molecular, in order to find possible common pathological mechanisms. Common
clinical features (e.g. increased infection rates, incidence of tumors and cardiovascular diseases) of SLE-patients and elderly
individuals and shared characteristics of immuno-senescence and SLE are identified. These similarities are strongest
in the adaptive immune system, where terminally differentiated T-cells and an immunological risk profile are found in
both conditions. Also the aging innate immune system has overlapping features with SLE, exemplified by a generally
lowered phagocytic capacity. However, great disparities between the aging immune system and SLE become apparent on
a closer look, affecting numbers, phenotype and function of most immune cells, ranging from NETosis by granulocytes to
the mechanisms underlying abnormal IL-2 production by T-cells. On the molecular level, also the increased presence of
aging mechanisms like telomere attrition, DNA damage, autophagy and the characteristics of the mTOR pathway in SLE,
possibly contributing to the shared changes on the cellular and clinical level are elaborated. The possible implications
thereof concern existing (hydroxychloroquine, rapamycine, Glucocorticoids) as well as novel therapeutic strategies targeting
more specific pathways which might rapidly reach the clinical arena.
Overall a differential view on the similarities of aging and SLE and possible consequences is presented.
Keywords: Aging, autophagy, immunosenescence, lymphocytes, mTOR, systemic lupus erythematosus, telomerase, telomere.
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