Anti-aging drug has a Catch… but not for Long

Dietary restriction holds the key to longevity. It’s no secret that as you drastically reduce calories, your metabolism will slow down with it [ask anyone who’s tried to crash diet about that one]. Science has been trying to crack that egg for awhile now and because of that, it is the most researched method for slowing down the aging process. That was why researchers were so excited to find that a drug — rapamycin — appears to mimic that anti-aging effect.

Rapamycin, an antibiotic and immunosuppressant approved for medical use about 15 years ago, has drawn extensive interest for its apparent ability — at least in laboratory animal tests — to emulate the ability of dietary restriction in helping animals to live both longer and healthier. If the name sounds familiar that is because rapamycin is primarily used as an immunosuppressant — to help prevent rejection — specifically for people who have had organ transplants.

However, this medication has some drawbacks. One of the big problems is an increase in insulin resistance that could set the stage for diabetes. But a new study offers some help to explain why that happens, and what could be done to address it.

The researchers suggest that a combination of rapamycin and another drug to offset that increase in insulin resistance might provide the benefits of this medication without the unwanted side effect.

“This could be an important advance if it helps us find a way to gain the apparent benefits of rapamycin without increasing insulin resistance,” said Viviana Perez, PhD, an author on the new article and an assistant professor in the Department of Biochemistry and Biophysics in the Oregon State University College of Science. “It could provide a way not only to increase lifespan but to address some age-related diseases and improve general health.”

Age-related diseases include many of the degenerative diseases that affect billions of people around the world, it is no surprise then that these are also among the leading causes of death: cardiovascular disease, diabetes, Alzheimer’s disease and cancer.

Laboratory mice that have shown rapamycin have reduced the age-dependent decline in spontaneous activity, demonstrated more fitness, improved cognition and cardiovascular health, had less cancer and lived substantially longer than mice fed a normal diet.

I’m sure you are thinking that’s fine and dandy but how does this work? Well rapamycin inhibits a biological pathway that is found in almost all higher life forms. That pathway might sound familiar too, it is the mTOR pathway. This pathway helps organisms avoid too much cellular expansion and growth when energy supplies dwindle.

[Loony Hint: mTOR stands for, you might have guessed mammalian target of rapamycin, okay maybe you wouldn’t have guessed that, but now you know.]

“Dietary restriction is one of the few interventions that inhibits this mTOR pathway,” Perez said. “And a restricted diet in laboratory animals has been shown to increase their lifespan about 25 to 30 percent. Human groups who eat fewer calories, such as some Asian cultures, also live longer.”

As I’ve been saying a big drawback to long-term use of rapamycin, is the increase in insulin resistance [which has been observed in both humans and laboratory animals]. The new study helped to identify why that is happening. Both dietary restriction and rapamycin inhibited lipid synthesis [creation of fat], but only dietary restriction increased the oxidation of those lipids in order to produce energy [turning fat into energy].

Rapamycin, by contrast, allowed a buildup of fatty acids and eventually an increase in insulin resistance, which in humans can lead to diabetes. Never fear since there are solutions to that problem, metformin can address that concern, and as a bonus is already given to some diabetic patients to increase lipid oxidation. To add to this, in lab tests, the combined use of rapamycin and metformin prevented the insulin resistance seen from using rapamycin alone.

If this research pans out, we could very well see the average age of humans surpass 100 years. I know personally, I worry that when I get older my quality of life will go down. Really, what is the point of a long life if I cannot enjoy it? So here is hoping that it is as simple as combining two drugs and giving us all more time to enjoy life.

Want to spend some of that longer life learning more? Then you might want the full study, which can be found —here!

Sources:
Yu Z, Wang R, Fok WC, Coles A, Salmon AB, & Pérez VI (2014). Rapamycin and Dietary Restriction Induce Metabolically Distinctive Changes in Mouse Liver. The journals of gerontology. Series A, Biological sciences and medical sciences PMID: 24755936