Introduction

The term replicative senescence describes the observation that normal eukaryotic cells cultured in vitro can attain a maximal number of population doublings proportional to the life span of the species and inversely proportional to the age of the individual (Handbook chapter 4). Cells can transgress this Hayflick limit to immortalization by viral transformation, for example, by transfection with the SV40 T protein. Analysis of the T protein showed that the immortalizing effect specifically could be ascribed to the C-terminal ATPase module. Hypothetically it was suggested that this ATPase module somehow could replace—or by transactivation of the ATP-synthase gene—compensate for a functional defect of the beta-subunit of the mitochondrial F1-ATPase: the master of ATPases serving the reverse function of producing ATP, the universal currency of free energy (Kroll, 1994). Support for this suggestion was gained from observations of exposure of the catalytic beta-subunit of the ATP synthase on the surface of different tumor cell lines, indicating an overexpression of this ATPase module in some immortalized cell lines (Kroll, 1996).

The ATPase module is an important subunit also in other essential cellular machines such as the membrane pumps and the heat shock proteins/molecular chaperones. That the SV40 T-protein was recognized as a molecular chaperone gave rise to the suggestion that this property might contribute to the general increased in vitro life span and occasional immortalization observed in cells trans-fected with the SV40 T-protein. This suggestion gained support from the observation that a similar increase in cellular life span in vitro could be obtained by transfec-tion with other chaperones or by heat shock or hormetic procedures raising the cellular level of expression of the heat shock proteins. The probable importance of the molecular chaperones for the process of cellular immortalization also appears from the observation that an increase in the level of expression of molecular chaperones is a common feature of the various procedures used to attain immortalization of primary cells in vitro, as well as from the frequent hyper-expression of various chaper-ones in immortal cancer cell lines, as in the inherently immortal primary cell lines from catfish (Kroll, 2002). The recognition that the SV40 T-protein as the human homologue p68 are DEAD box RNA-chaperones and the Werner Protein WRN probably is a RecQ DNA-chaperone places some emphasis on the importance of the RNA/DNA-chaperones in the definition of cellular longevity (Kroll, 2004). Accordingly evidence has been presented to suggest that the evolution of longevity depends on alterations in the expression of relatively few regulatory genes (Kroll, 2005). This chapter presents evidence on the probable importance of the molecular chaperones as antagonists of the aging process and for the evolution of cellular and species longevity.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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