Dr. Nelson's research aims to understand the genetic and physiological
basis for aging, using nutritional and pharmacologic interventions that
extend rodent lifespan as probes. Most recently, his laboratory
discovered dramatic genetic variation in the lifespan response to
dietary restriction, including a life-shortening effect in some
genotypes. These findings provide a new way of identifying the genes and
probing the mechanisms whereby dietary restriction and other
interventions affect aging. For example, his group found that
maintenance--not reduction--of adiposity was a strong correlate of
lifespan extension, whereas reduction in adiposity was a risk factor for
life shortening by dietary restriction. His research also focuses on
the role of endocrine systems in aging, with a particular emphasis on
the role of hyperadrenocorticism and insulin signaling in the
life-extending effect of dietary restriction. In addition, the
NIA-funded Interventions Testing Center in which he participates has
discovered lifespan- and heathspan-extending effects of several
compounds with potential clinical application, including rapamycin, an
FDA-approved inhibitor of mTOR signaling.
Harrison DE, Strong R, Allison DB, Ames BN, Astle CM, Atamna H,
Fernandez E, Flurkey K, Javors MA, Nadon NL, Nelson JF, Pletcher S,
Simpkins JW, Smith D, Wilkinson JE, Miller RA. Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell. 2014 Apr;13(2):273-82.
Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors
MA, Li X, Nadon NL, Nelson JF, Pletcher S, Salmon AB, Sharp ZD, Van
Roekel S, Winkleman L, Strong R. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell. 2013 Dec 17.
Nelson JF, Strong R, Bokov A, Diaz V, Ward W. Probing the relationship between insulin sensitivity and longevity using genetically modified mice. J Gerontol A Biol Sci Med Sci. 2012 Dec;67(12):1332-8.
Liao CY, Rikke BA, Johnson TE, Gelfond JA, Diaz V, Nelson JF. Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell. 2011 Aug;10(4):629-39.
Liao CY, Rikke BA, Johnson TE, Diaz V, Nelson JF. Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. Aging Cell. 2010 Feb;9(1):92-5