Saturday, February 2, 2013

The Longevity Gene

A new study published on January 31, 2013 in the journal Cell Reports (1) found that by infusing the blood stem cells of old mice with a so-called “longevity gene,” SIRT3, they were able to rejuvenate their regenerative potential, in effect to become younger.

SIRT3 is a protein among a class known as sirtuins which are known to regulate the aging process. SIRT3 is found in a cell’s mitochondria, which has its own DNA apart from that of the nucleus. Previous studies have shown that the SIRT3 gene is activated during caloric restriction, and that caloric restriction extends lifespan in some species, though that hasn’t yet been shown in humans.

Studies have shown that having an extra copy of another sirtuin, SIRT2, extends the lifespan of yeast, worms and flies. (2) In mammals there are now known to be at least seven sirtuins (SIRT1-SIRT7).
In a recent study, mice with an over-expressing SIRT2 have been shown to have an increased lifespan. This present study is the first to show that sirtuins can reverse age-associated degeneration.

Activating Antioxidants
Stem cells are tissue-specific cells that allow for self-renewal and which persist throughout an organism’s lifespan. Stem cell aging is thought to be the result of an accumulation of cellular and genomic damage caused by oxidants resulting from cellular respiration. SIRT3 increases the activity of antioxidants which promote the scavenging of these damaging oxidants. In aging organisms SIRT3 levels are lower than in young organisms. This study shows that by increasing the levels of SIRT3 in aged hematopoietic stem cells they can be rejuvenated.

Freezing Fetel Cells
A separate study (3) has shown that old stem cells can be rejuvenated by placing them in a young microenvironment, raising the possibility that a person’s own stem cells may one day be banked and rejuvenated to treat their age-related disease or extend lifespan. Even more intriguing, a recent study (4) has shown that fetal stem cells are found in the placenta, which is usually discarded. These fetal stem cells are pluripotent—they can differentiate into different cell types—and have the characteristics of young (nine-month-old) cells, including young mitochondria. They can be frozen to be later used to treat adult degenerative disease or increase longevity.

One such possible treatment is in stroke patients. It has recently been shown (5) that stem cells can significantly increase recovery from stroke in rats irrespective of the origin of the stem cells (either fat or bone marrow stem cells were used). The treated rats had higher levels of biomarkers associated with brain repair, even though the stem cells were not shown to migrate to the damaged area of the brain.

Cure Aging?
The study of biological aging is proceeding on many fronts. It is clear that the aging process is closely related to our genome as a species—each species has a unique lifespan. There are many theories of biological aging and the evolutionary process that has brought us to this point, topics that I will address in future posts. What is clear is that in the foreseeable future, we will find a way of significantly increasing our lifespan. It may even be possible to “cure” the “disease” of aging, though that may be in the distant future. Before we get there, however, we as a society have to decide if we want a nearly “immortal” society. The consequences are vast: biologically, in terms of our evolution as a species; with respect to our ability to feed a vastly larger population; and in terms of the kind of society we would construct to control such things as procreation, equal distribution of longevity throughout the world’s populations, structure of governments, structure of power (you don’t want the same boss for 100 years), ethical concerns, etc. Stay tuned.

1. Brown, Katharine et al., SIRT3 Reverses Aging-Associated Degeneration. Cell Reports, 2013; DOI: 10.1016/j.celrep.2013.01.005
2. Guarente, L. (2007). Sirtuins in aging and disease. Cold Spring Harb. Symp. Quant. Biol. 72, 483–488.
3. University of Texas Health Science Center at San Antonio (2011, November 1). Personal stem cell banks could be staple of future health care. ScienceDaily. Retrieved February 2, 2013.
4. Nazarov, Igor, et al., Multipotent Stromal Stem Cells from Human Placenta Demonstrate High Therapeutic Potential. Stem Cells Trans Med, May 8, 2012 DOI: 10.5966/sctm.2011-0021
5. Gutierrez-Fernandez, Maria, et al., Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke. Stem Cell Research & Therapy, 2013; 4 (1): 11 DOI: 10.1186/scrt159