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Accumulation of Dolichol in Older Tissues Satisfies the Proposed Criteria To Be Qualified a Biomarker of Aging

Centro Interdipartimentale di Ricerca di Biologia e Patologia dell'Invecchiamento dell'Università degli Studi di Pisa, Scuola Medica, Pisa, Italy.

Address correspondence to Ettore Bergamini, MD, PhD, Professor, Centro di Ricerca di Biologia e Patologia dell'Invecchiamento, Via Roma 55–Scuola Medica, 56126 Pisa, Italy. E-mail: ebergami{at}med.unipi.it

Criteria for defining biomarkers have been suggested. Accumulation of dolichol in tissues of older animals meets the following criteria: (a) levels of dolichol exhibit a quantitative correlation with age in all tissues and are not altered by several age-dependent diseases in the same direction as that of aging; (b) accumulation is not secondary to metabolic changes of aging and is altered appropriately by factors that modulate the aging rate like caloric restriction and physical exercise; (c) biomarker is applicable to different tissues across mammalian species, including humans, and to trisomy 21 and its hypothalamic digoxin-mediated model. Reliable changes in tissue dolichol levels are seen in relatively short intervals of time compared to over a life span, and levels can be tested on a small amount of tissue without causing death of the animal. In this article, we show applications to the study of host–graft interaction and detection of gender-related differences in biological age, and we discuss mechanism(s) of accumulation.