Mitochondrial Cause of Aging Can Be Reversed

Researchers have found a cause of aging in lab animals that can be reversed, possibly providing an avenue for new treatments for age-related diseases including type 2 diabetes, cancer, muscle wasting, and inflammatory diseases.

The researchers plan to begin human trials late 2014. The study, which was published December 19, 2013, in the journal Cell, relates to mitochondria.

The research led by geneticist David Sinclair from Harvard Medical School (Boston, MA, USA) discovered a sequence of molecular events that enable communication inside cells between the mitochondria and the nucleus. As communication breaks down, aging accelerates. “The aging process we discovered is like a married couple—when they are young, they communicate well, but over time, living in close quarters for many years, communication breaks down,” stated Prof. Sinclair. “And just like a couple, restoring communication solved the problem.”

The hypothesis behind the research is that as humans age, levels of the chemical nicotinamide adenine dinucleotide (NAD), which begins this communication cascade, decline. Until now, the only way to suppress the NAD decline was to curb calories and exercise intensively. In this study, the researchers used a compound that cells convert into NAD to repair the broken network and rapidly restore communication and mitochondrial function. It mimics the effects of diet and exercise.

While Prof. Sinclair’s group in Boston was working on muscles in tissue culture, colleagues from the University of New South Wales (UNSW; Sydney; Australia) were working on animal models to validate the research that could have the same findings. “It was shocking how quickly it happened,” said coauthor Dr. Nigel Turner, from UNSW’s department of pharmacology. “If the compound is administered early enough in the aging process, in just a week, the muscles of the older mice were indistinguishable from the younger animals.”

The mice, which were two-years-old, also performed well on insulin resistance and inflammation—both of which are correlated with aging. They were compared with six-month-old animals. “It was a very pronounced effect,” stated Dr. Turner. “It’s something like a 60-year-old being similar to a 20-year-old on some measures.” The younger mice given the same compound were “supercharged above normal level” on certain measures, according to Dr. Turner. “So it is possible this would have benefits in healthy, young humans.”

One notably significant facet of this research involves HIF-1, which is an intrusive molecule that foils communication, but also has a role in cancer. It has been known for some time that HIF-1 is turned on in many cancers, now this research has found it also switches on during aging. “We become cancer-like in our aging process,” noted Prof. Sinclair. “Nobody has linked cancer and aging like this before.” This may clarify why the greatest risk of cancer is age.

The researchers are now examining the longer-term outcomes the NAD-generating substance has on mice. They are exploring whether it can be used to safely treat rare mitochondrial diseases and other conditions, such as type 1 and type 2 diabetes, as well as for longevity and good health.

Prof. Sinclair and his group have been studying the fundamental science of aging for many years, primarily focusing on a group of genes called sirtuins. Earlier research from his laboratory had demonstrated that one of these genes, SIRT1, was activated by the naturally occurring compound resveratrol (found in small amounts in grapes, red wine, and various nuts).

The latest research goes further, as it triggers all seven of the sirtuin genes. “There’s clearly much more work to be done here, but if those results stand, then aging may be a reversible condition, if it is caught early,” concluded Prof. Sinclair.

Related Links:
Harvard University Medical School
University of New South Wales