Cellular senescence is a central component of the aging process. This cellular response has been found to be induced by multiple forms of molecular damage and senescent cells increase in number with age in all tissues examined to date. We have examined the correlation with age of two key proteins involved in the senescence program, p16INK4a and HMGB2. These proteins are involved in cell cycle arrest and chromatin remodeling during senescence. Circulating levels of these markers increases with age and correlates with functional status. The levels of HMGB2 appear to be significantly correlated with functional status, whereas p16INK4a levels are more weakly associated. Interestingly, there is a strong correlation between the two proteins independent of age. In particular, a single high-functioning individual over 90 years of age displays a disproportionately low level of HGMB2. The results suggest that with improved testing methodology, it may be possible to monitor circulating protein markers of senescence in human populations.