Sickle cell disease as an accelerated aging syndrome

Abstract

Sickle cell disease (SCD) is characterized by vaso-occlusion, hemolysis, and systemic manifestations that form the hallmark of the disease. Apart from morbidity, SCD is also associated with increased mortality and decreased quality of life. Aging is a natural phenomenon that is associated with changes at cellular, tissue, and organ levels, in addition to the loss of physical fitness, increased susceptibility to diseases, and a higher likelihood of mortality. Some of the cellular mechanisms involved in normal (or physiological) aging include abnormalities of sphingolipids (ceramides) and reduced length of the telomere. These changes have also been documented in SCD. Cellular, organs, and physical manifestations of SCD resemble an accelerated aging syndrome. Sickle erythrocytes also acquire morphological features similar to that of aged normal erythrocytes and are thus picked up early by the macrophages for destruction. Brain, kidney, heart, innate and adaptive immune system, and musculoskeletal system of patients with SCD exhibit morphological and functional changes that are ordinarily seen in the elderly in the general population. Stroke, silent cerebral infarcts, cardiomegaly, heart failure, pulmonary hypertension, nephropathy with proteinuria, osteopenia, osteoporosis, osteonecrosis, gout, and infections are exceedingly common in SCD. In this review, we have attempted to draw parallels between SCD and accelerated aging syndromes.

No crystal stair: supporting fertility care and the pursuit of pregnancy in women with sickle cell disease

“…Age-based thresh olds for infer til ity diag no sis may not apply to women with SCD, who have a sharper tra jec tory of decline in ovar ian reserve. [18][19][20][21][22] At Johns Hopkins, we offer repro duc tive endo cri nology and infer til ity (REI) spe cial ist con sul ta tion to women who have attempted to con ceive for 6 months or lon ger. Helping patients know when to seek care can help with timely REI referral; rec og nized bar ri ers to infer til ity care make atten tion to referral tim ing espe cially impor tant.…”

“…26 This might be expected in a dis ease asso ci ated with accel er ated aging and sup ports the hypoth e sis that women with SCD have a narrower repro duc tive win dow than unaf fected women. 22 As infer til ity risks may accrue at a youn ger age in women with SCD than in unaf fected women, tests to mea sure ovar ian reserve may help direct care (Table 2). 25 When nor mal, ovar ian reserve mea sures do not pre dict fer til ity-that is, the abil ity to become preg nant.…”