Factors in the blood that affect the behavior of tissues in beneficial ways are a popular topic in aging research at the moment. Researchers are beginning to identify proteins whose amount in circulation changes in reaction to rising levels of damage in aging, and which if altered in old animals can partially reverse some aspects of age-related decline in tissue function. Aging is one set of changes, but what about other differences between individuals such as the beneficial changes to the operation of metabolism brought on by calorie restriction? Researchers would very much like to recreate calorie restriction benefits without the need to eat less, and as a result of findings elsewhere the approach of altering levels of various factors in the blood is now getting a second look. The example quoted here is a study in cell cultures only, but is still somewhat interesting:
The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts.
While all of the reported CR-mediated effects in vitro have been observed after incubation of cells for short periods with CR sera from various species, little is known about the long-term effects of CR serum treatment in cultured cells. An important cellular consequence of the process of ageing is replicative senescence, whereby cells lose their replicative capacity and irreversibly exit the cell cycle. Decreased senescence in vivo is believed to contribute to delayed ageing and the increased tolerance to stress observed in organisms subjected to CR regimens; however, the study of this cellular process in vivo (either in animals or humans) is experimentally challenging. Therefore, we decided to test the effects of CR serum on cellular senescence in vitro using normal human diploid fibroblasts, which undergo replicative senescence after several passages in culture.
We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes.