Vol. 23, Issue 1: Fall 2015

Research in Reverse Aging

Yash Shah

In the sixteenth century, Ponce de Leon dedicated the rest of his life to search America for the Fountain of Youth. Although he never found it, researchers studying aging are finding that certain techniques have been found to minimize the aging effect. Harnessing and using this research could have extensive applications in the real world, who doesn’t want to stay young?

It is strange to think about how and why aging occurs, despite being such a common part of our lives. The Villeda Lab at UC San Francisco is tackling these questions. In one of its most recent publications the lab shows that certain proteins circulating in an organism’s blood slow down aging. These researchers explain that systemic manipulations such as exercise, caloric restriction, and changing blood composition can stop and potentially reverse many effects of aging, especially age-related loss of plasticity in the brain. Although genetic influences do largely affect how one will grow, studies show a surprising level of malleability in an organism’s lifespan.

The research group explored how much of a role genetics plays in aging. Through numerous studies, it has been found that an organism’s lifespan can be affected at a molecular level; this is through complex interactions and relationships between many different genes. They are usually involved in cellular processes such as homeostasis; also, many pro-longevity signaling pathways have also been shown to play important roles in higher-level brain function. Therefore, there is evidence for a connection between the variability in aging and the plasticity of the Central Nervous System (CNS) after time. In fact, it shows that because the CNS is intimately involved in every other aspect of the body, it is in the unique position of potentially being influenced by and influencing the plasticity of the rest of the body. Gene therapy does not seem to be a viable option because there is not a specific genetic target.

However, an alternative, more systemic approach to could be just as successful, according to researchers at UCSF. Broad changes in the systemic environment (such as blood composition), rather than point manipulations in the CNS, may provide the means for rejuvenation. This can be done through exercise, CR, and changes in blood composition by heterochronic parabiosis or young plasma administration.

One feature common among aging tissues is loss of regenerative capacity, and the maintenance of adult stem/progenitor cells which have the ability to self renew and produce new cells in adult tissue is critical in preserving this capacity.

Exercise seems to be a method through which aging can be slowed or reversed. Physical exercise increases blood delivery to most tissues, which leads to change in the systemic environment. It also affects molecular and cellular processes that play major roles in stem cell function both in vitro and in vivo. This is because exercise induces autophagy, the clearance of cellular debris, which protects hematopoietic stem cells from metabolic stress. It has also been shown to enhance neural progenitor proliferation and neurogenesis to a higher level. In the blood, circulating levels of IGF-1 decrease with age but systemic manipulations seem to restore these levels to previous standards. Together, these factors show the ability research has in rejuvenating adult stem cell function across tissues.

In addition, caloric restriction also provides a method for systemic manipulation that successfully can reverse the effects of aging, through a reduction of 20-40% of caloric intake without malnutrition. This effect can be attributed to increasing glucose metabolism, reducing oxidative stress, and the increasing ability of cells to counteract DNA damage as well as influencing aspects of the aging immune and neuroendocrine system. Caloric restriction has also been shown to rejuvenate tissue regeneration through mechanisms similar to what happens through exercise. This occurs by the release of steroids by the body in response to caloric restriction or exercise.

Finally, heterochronic parabiosis, which is a process by which the blood streams of two organisms are connected, can also have the same effect as exercise and caloric restriction. The effects that the blood of younger animals can have on the physiology and behavior of older animals when transfused to them have been found to be significant. Through this model it has been shown that exposure to young blood can enhance the regenerative capacity of peripheral tissues and CNS in aged animals. “Pro-youthful” factors in the younger blood are credited for the physiological and behavioral changes. It has been shown that these factors change the systemic environments for the tissues of the body, reversing the effects of aging upon them. This is done by restoring growth factors such as GDF11 to more youthful states which has been shown to reverse age-related muscular and cardiovascular impairments in mice. It has also been found that daily administration of recombinant GDF11 increases tissue function.

Though seemingly impossible, the reversal of aging is becoming more realistic. However, these findings do not contain the root cause or causes of aging, and as such there is no existing “cure” to aging. This research does promise extension of life through personal health and heterochronic parabiosis.