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T-Kininogen: A Biomarker of Aging in Fisher 344 Rats With Possible Implications for the Immune Response

¹ Instituto de Ciencias Biomédicas, Programa de Biología Celular y Molecular, Facultad de Medicina, Universidad de Chile, Santiago.
² Centro FONDAP de estudios moleculares de la célula, Facultad de Medicina, Universidad de Chile, Santiago.
³ Lankenau Institute for Medical Research, Wynnewood, Pennsylvania.
⁴ Department of Bioscience and Biotechnology, Drexel University, Philadelphia, Pennsylvania.

Address correspondence to Felipe Sierra, PhD, National Institute on Aging, 7201 Wisconsin Ave., Suite 2C231, Bethesda, MD 20892. E-mail: sierraf{at}nia.nih.gov

T-kininogen (T-KG) is a reliable biomarker of aging in male Sprague-Dawley rats. Here we confirm, in a longitudinal study, a similar behavior in Fisher 344 rats of both sexes. In males, the increase in serum levels of T-KG follows an exponential curve, whereas in females the increase is best fitted by a linear curve. In both genders, dietary restriction delays the increase in T-KG. We have previously shown that T-KG inhibits T lymphocyte proliferation. Here we show that serum T-KG levels correlate negatively with the ability of splenocytes (most likely B cells) to proliferate in response to lipopolysaccharide. A similar correlation was not observed with other markers of inflammation, including 1-acid glycoprotein (AGP), haptoglobin, or interleukin-10. We conclude that the increase in serum T-KG represents a useful biomarker of aging in Fisher 344, and it correlates with decreased lymphocyte proliferation with age, although a cause–effect relationship has not been established.