Reduced expression levels of the senescence biomarker clusterin/apolipoprotein j in lymphocytes from healthy centenarians.

Clusterin/apolipoprotein J (CLU) is a conserved, ubiquitously expressed secreted glycoprotein that has been implicated in several physiological processes and was found to accumulate in many severe physiological disturbances. We have previously shown that the CLU gene and protein are upregulated during replicative senescence, stress‐induced premature senescence, in vivo aging, and in several age‐related diseases. In this study we have examined the CLU gene relationship to human longevity. We recruited and further analyzed 96 blood samples from Italian and Greek healthy donors of different ages, including 49 centenarians. We found that although the CLU gene expression levels increase during aging, in the centenarians' samples CLU levels were lower than those found in old donors. We then investigated the possible existence of a genetic polymorphism related to longevity at the CLU structural locus. A neutral noncoding sequence variant was detected 35 nucleotides upstream from exon 6, which does not correlate, however, with the age of the donor. We conclude that CLU gene accumulation during in vivo aging does not directly relate to chronological age, but rather indicates increased levels of organismal stress due to a progressive failure of homeostasis and/or to prolonged exposure to a stressful environment.