=================== The Cause of Ageing ===================
:Abstract: Ageing is an incredible plastic process which can be speeded up, slowed down, stopped and even reversed. Understanding its very nature will enable us to manipulate ageing effectively for the health and well-being of humans. Unlocking the capacity for rejuvenation will be the most potent way. Lifespan extension by dietary restriction is the most powerful non-genetic intervention acting on the ageing process and may provide us with the hint on the cause of ageing.
Why we age? This is a fundamental question of crucial importance as it deals with the cause of ageing and when answered correctly would subsequently make it possibly to find interventions with unpredictable health benefit for mankind. Recent data showed that age-related changes can be reversed by simple activating a single transcription factor (Unal et al., 2011). Therefore, ageing is not simple due to the irreversible accumulation of age-related damage and the reversal of ageing is not any more theoretical impossible. It might be argued from an evolutionary perspective that ageing is simple due to the lack of natural selection forces after reproduction. Changes which are beneficial early in life may become detrimental later in adulthood (antagonistic pleiotropy). There is even evidence for programmed ageing operating on the level of group selection, hence altruism (Fabrizio et al., 2004). Strikingly, the involved pathways include nutrient sensing as well as growth regulation and are evolutionary well conserved. In light of this view, ageing is a process speeding up evolution by ensuring generational turnover and gives a great advantage to a population in a natural environment which changes. We age because the environment is changing. Nothing in evolution makes sense except in the light of population genetics. Dietary restriction (DR) extends lifespan in multiple species. It might be an evolutionary conserved response to famine, slowing down ageing and reproduction in order to be able to reproduce when resources are again plentiful. The lifespan-prolonging effect of DR can be abrogated by genetic interventions of DR-essential genes. Whatever the mechanisms of DR is, it needs to be deciphered as it the most powerful non-genetic intervention to retard ageing and as it appears to affect the basic ageing process itself it might give clues to the actually cause of ageing.
Reversed mortality rates of Drosophila melanogaster that have been switched to DR are a consequence of a reversal of the damage (Mair et al., 2003). The ability of repair and replacement systems to reverse the damage accumulated since birth so rapidly argue that organisms normally maintain a sub-optimal level of protection (Longo et al., 2005). Yeast undergoes an age- and pH-dependent death with features of mammalian apoptosis. After 90-99% of population dies, a small mutant sub-population uses nutrient released by dead cells to grow. Adaptive regrowth is inversely correlated with protection against superoxide toxicity and lifespan and is associated with elevated age-dependent release of nutrients and increased mutation frequency. Ageing together with relatively high mutation frequency can result in a major advantage in adaptation to changing environments. Yeast organisms undergo an altruistic and premature ageing and death program, mediated in part by superoxide (Fabrizio et al., 2004).