A Focus on Regulatory Systems in Aging
Much of modern aging research, too much in my view, focuses on regulation of aging and the prospects for changing regulatory processes to modestly slow the progression of age-related frailty and disease. Aging is caused by the accumulation of a few types of cellular and molecular damage and so these regulatory processes and their changes in aging are largely reactions to that damage. They are the wrong place to be intervening for best effect, and the focus should instead be on repair of the root cause damage. That remains a minority view at this time, unfortunately, which is why it is so important to raise enough funding to produce definitive proof of its greater effectiveness as a basis for therapies.
This paper is more indicative of how a majority of researchers think about the situation, however. This view explains why those interested in enhancing longevity are most often found working on expensive, marginal ways to alter the very complex reaction to damage rather than addressing the damage itself:
In the consideration of life-extending effects of aging-modulating drugs, a logical error can occur as a result of reductionist thinking peculiar to gerontologists in the middle of the last century when major aging theories including the free radical theory of aging were proposed. From the reductionist point of view, the organism was considered as a sum of relatively independent processes and mechanical components, and interventions designed to prolong life were seen as those being similar to car repairing. If this were indeed the case, then it would be possible to slow the rate of aging by affecting molecular pathways that influence specific aspects of aging, analogous to how antioxidants can slow down the rate of aging of plastic.However, by summarizing the accumulated information, one can conclude that a reductionist approach in experimental gerontology has proved rather ineffective until now. This is not surprising, since aging is a classic "complex trait," in other words, a trait that is influenced by a plurality of genetic pathways. For example genome-wide research in Drosophila shows that hundreds of genes are involved in the control of aging. Therefore, it seems very difficult, if not impossible, to develop effective pharmaceutical interventions that may slow aging and extend longevity by targeting single genetic pathways.
On the contrary, more modern systemic ("holistic") thinking considers the organism as a whole. Taking into account the complexity of the aging process, the systemic approach addressed primarily to central regulation mechanisms seems more appropriate to developing aging-modulating treatments. From a systemic point of view, aging is not a disease in the sense of being caused by disturbance in several specific pathway(s), but is rather an inevitable consequence of realization of some (probably still substantially unknown) central regulatory processes making the organism more vulnerable to disease with age. According to these conceptual frameworks, the aging process is not primarily a result of accumulation of stochastic damage but is rather a co-product of developmentally regulated processes.
One potential mechanism of central regulation of the whole life cycle including aging is a process of epigenetic control of gene expression having important features in the given context. Indeed, it is: (1) potentially adaptive; (2) linking development and aging; (3) generalizing at the whole-organism level.