Our research has focused on assessing the possible role oxidative stress may have as an initiator of aging and on mechanisms reducing oxidative stress as possible determinants of longevity. Methods to detect and measure oxidative damage are essential to these studies. We have developed a new assay to measure total oxygen radical absorption capacity (ORAC) of serum. Using this assay, we have found that the ORAC value of serum increases in direct proportion to life span of different mammalian species but appears not to change with age. The spin-trap agent, N-tert-butyl-alpha-phenylnitrone (PBN) has been reported to reverse a number of age-related effects, including a decrease in oxidative stress state. Preliminary results in our laboratory indicate that PBN may stimulate molecular renewal rate in old animals and possibly extend life span. We have not been able to detect any age related changes in alkaline protease activity nor its stimulation by PBN. However PBN when given orally to mice does have some effect in increasing mean life span. PBN and other related spin traps were found to release nitric oxide in vitro and stimulate guanylate cyclase activity after reacting with a free radical. Thus the mechanisms of PBN action may involve delivery of nitric oxide to specific neurological sites in the brain.
| Tilstra, Jeremy S; Robinson, Andria R; Wang, Jin et al. (2012) NF-?B inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest 122:2601-12 |
| Lavasani, Mitra; Robinson, Andria R; Lu, Aiping et al. (2012) Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat Commun 3:608 |
| Vo, Nam; Seo, Hyoung-Yeon; Robinson, Andria et al. (2010) Accelerated aging of intervertebral discs in a mouse model of progeria. J Orthop Res 28:1600-7 |
| Bhagwat, Nikhil R; Roginskaya, Vera Y; Acquafondata, Marie B et al. (2009) Immunodetection of DNA repair endonuclease ERCC1-XPF in human tissue. Cancer Res 69:6831-8 |
