Dear dr Metaxas, any researcher involved in research hopes to obtain breakthrough results. But, would wait for evaluation by the readers of its work qualifying them a breakthrough or ...not.

We have concluded in last months of 2013 a life span study in mice, where 5 different isocaloric, isonitrogenous diets differing only for the quality of nitrogen content were compared. Although results cannot be anticipated to publication, I may say results were both inexpected and haunting. We have focused peculiarly on controls of autophagy and apoptosis into cells of many different organs. Morphological, hystochemical, molecular differences related to time necessary for aging, and therefore life span, were indagated, and a complex hyerarchy of how aging is controlled by different organs has been observed. Aging is a physiological process primarily ruled by...soon the answer!

You may see many paradigms erased by this answer, by the way!

If those data will be a breakthrough or not, will be decided by our collegues, as usual. Obviously, we hope so.

Start looking for the connection between sleep and aging. Recent research (last couple years) has seen sleep studies overlapping with anti-aging more and more.

There is a big connection between the rest/hibernation phase of life (at all scales - yeast, worms, flies, mice, and primates) and cellular ROS damage.

The narrative that I've come up with is that you can think of your brain as a CPU that's being overclocked during the day. At night, it shuts down and cools off, repairing itself and cleaning out the buildup of ROS. Sirtuin agonists and sirtuin-like molecules (a lot of plant polyphenols) enhance this process, but only at night. This narrative explains a lot of the current findings relating to mitochondrial redox chemistry, sirtuin activation of cellular stress response, and anecdotal evidence like the French paradox and mediterranean diet.

My advice - drink red wine and eat dark chocolate right before going to sleep so you metabolize the resveratrol overnight, don't miss sleep, and don't force yourself to stay awake at night. Plant foods (vegetables, plant oils, etc.) typically contain hormesis agents in the form of polyphenols which should be consumed in such a way as to be metabolized overnight or when resting.

Is ageing a non-programmed phenomenon (the effect of the accumulation of various damages) or a programmed phenomenon (i.e., genetically determined and regulated, and favoured in terms of supra-individual selection)?

The current opinion is the first option, but I think that evidence and theoretical arguments are strongly against the first and in support of the second option.

In the first case, senescence is hardly tameable, while the opposite is true in the second case.

You may find papers about this topic in my personal page (www.r-site.org/ageing) and in a specific page of the site www.programmed-aging.org, i.e. www.programmed-aging.org/theory-2/aging_theory_chronology.html.

In particular, please,see:

 1998 - Telomerase introduction in somatic cells makes them able to innumerable duplications and reverts manifestations of cell senescence (Bodnar et al. 1998, Counter et al. 1998 , Vaziri & Benchimol 1998, de Lange & Jacks 1999) 

2011 - Telomerase reactivation in aged mice with artificially blocked telomerase shows a marked reversal of degenerative manifestations, even for nervous system (Jaskelioff et al. 2011)

and read:

G. Libertini (2009) The Role of Telomere-Telomerase System in Age-Related Fitness Decline, a Tameable Process, in Telomeres: Function, Shortening and Lengthening, Nova Science Publ., New York

G. Libertini (2009) Prospects of a Longer Life Span beyond the Beneficial Effects of a Healthy Lifestyle, in Handbook on Longevity: Genetics, Diet & Disease, Nova Science Publ., New York.

Let me know your considerations

Mr. Libertini, while I find the publications you cited thought-provoking and informative, I can't really think of any evolutionary pressures that would have selected for the hypothetical preliminary gene(s) for aging in a population. By the time the individual species started to go senescent, it will most likely have already passed on its genes. How will its offspring have any advantage carrying their "aging" gene over the other members of the population without the aging gene? The members of the population without the aging gene would have tremendous advantages and a longer time-period in their lifespan to breed and produce progeny, and therefore their relatives will have a greater proportion of representation in the population. While a self-destructive mechanism would keep population numbers low and potentially delay resource-depletion through over-population problems, both types of the species (the non-aging and the aging) are competing in the same pool of resources, which in itself acts to keep population numbers in check.

Dear Ana,

1) In the first Darwinian concept of natural selection, a gene is favoured when it determines a greater fitness for the survival or for the reproduction capacity of the individual having it (and, clearly a gene is contrasted by natural selection if it determines the opposite). Your argument is within this logic, which was corrected by the same Darwin, e.g. when he says: “A tribe including many members who … were always ready to aid one another, and to sacrifice themselves for the common good, would be victorious over most other tribes; and this would be natural selection.” (C. R. Darwin, The descent of man. John Murray, London 1871.

But, there are a lot of known phenomena where genes determine the death of an individual or of a close relative and that can be interpreted only within the logic of supra-individual selective mechanisms. Now, these phenomena are defined by the neologism "phenoptosis" (to which are dedicated thematic issues of Biochemistry Moscow).

(Please, read: G. Libertini, Classification of Phenoptotic Phenomena, Biochemistry Moscow, 2012, 77:707-715; you may find it on my personal page, www-r-site.org/ageing).

2) The question: Is aging (defined as "age-related fitness decline in wild condition") a phenoptotic phenomenon? And, if the answer is yes, which is the particular advantage for aging (clearly, in terms of supra-individual selection!), that is greater than its individual disadvantage?

Please, consider carefully the arguments and the evidence expounded in my 1988 paper: G. Libertini, An Adaptive Theory of the Increasing Mortality with Increasing Chronological Age in Populations in the Wild, J. Theor. Biol. 1988, 132, 145-162, and in the following works where the subject is deepened.

In these weeks, I will publish on Current Aging Science a paper where I confirm and widen the strong evidence in support of aging explained as phenoptotic phenomenon and against the opposite view. If you want, I will soon send a copy of it after the publication.