Fight Aging!

The recently announced Palo Alto Longevity Prize is split into two parts, with the second to be awarded for a demonstration that restores metabolic homeostasis in an aging mammal to that of a young mammal. The prize administrators picked heart rate variability as the surrogate measure of homeostasis, which is an interesting choice.

Here one of the longevity science advocates from the Russian aging research community suggests that heterochronic parabiosis could be a winning approach for this portion of the prize. This involves linking the circulatory systems of two animals, usually mice, one old and one young. In recent years this has been used to identify some of the changes in circulating proteins that are key to the behavior of stem cells and other aspects of our biology that change with age.

One of the most productive paradigms of aging suppression is based on rejuvenation of blood-borne systemic regulatory factors. Parabiosis, which is characterized by a shared blood supply between two surgically connected animals, may provide such experimental paradigm. We propose to use heterochronic parabiosis, the parabiotic pairing of two animals of different ages, for old mouse rejuvenation. Heterochronic parabiosis also provides an experimental system to identify systemic factors influencing the aging process of the old mouse and promoting its longevity. The probability of the proposed study to demonstrate significant improvement of the heart rate variability marker is extremely high, because parabiosis was already shown to promote functional parameters of the nervous and cardiovascular systems.

The optimum rejuvenation effect of heterochronic parabiosis can be achieved using genetically identical animals. Genetically identical non-model organisms of different age can only be obtained by cloning. Interestingly, that there are no investigations of heterochronic parabiosis of cloned animals. Heterochronic parabiosis experiments indicate that blood-borne signals from a young circulation can significantly impact the function of aging tissues. The implication of these findings is that old tissues might make their function almost as well as young tissues if, by means of systemic influences, the molecular pathways could be 'rejuvenated' from an old state to a young state.

At first we will perform cloning of adult (1-year-old) mice using technique for improved success cloning rate. The parabiosis will be established at the age of 18 months for old partners and 2 month for the young ones. The detailed life span assay will reveal the influence of heterochronic parabiosis with the young clone on cardiovascular, nervous, respiratory, skeletal and muscular systems. The lifespan assay will how the young clone parabiosis impact on longevity of older partner. In addition, systemic factors, which influence the aging process of the old mouse and promote its longevity and rejuvenation, will be revealed.

Link: http://mariakonovalenko.wordpress.com/2014/10/03/how-to-win-the-palo-alto-longevity-prize/