Researchers find a cause of aging that can be reversed

by David Cameron

Researchers have discovered a cause of aging in mammals that may be reversible.

The essence of this finding is a series of molecular events that enable communication inside cells between the nucleus and mitochondria. As communication breaks down, aging accelerates. By administering a molecule naturally produced by the human body, scientists restored the communication network in older mice. Subsequent tissue samples showed key biological hallmarks that were comparable to those of much younger animals.

"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," said Harvard Medical School Professor of Genetics David Sinclair, senior author on the study. "And just like with a couple, restoring communication solved the problem."

This study was a joint project between Harvard Medical School, the National Institute on Aging, and the University of New South Wales, Sydney, Australia, where Sinclair also holds a position.

The findings are published Dec. 19 in Cell.

Communication breakdown

Mitochondria are often referred to as the cell's "powerhouse," generating chemical energy to carry out essential biological functions. These self-contained organelles, which live inside our cells and house their own small genomes, have long been identified as key biological players in aging. As they become increasingly dysfunctional over time, many age-related conditions such as Alzheimer's disease and diabetes gradually set in.

Researchers have generally been skeptical of the idea that aging can be reversed, due mainly to the prevailing theory that age-related ills are the result of mutations in mitochondrial DNA—and mutations cannot be reversed.

Sinclair and his group have been studying the fundamental science of aging—which is broadly defined as the gradual decline in function with time—for many years, primarily focusing on a group of genes called sirtuins. Previous studies from his lab showed that one of these genes, SIRT1, was activated by the compound resveratrol, which is found in grapes, red wine and certain nuts.

Ana Gomes, a postdoctoral scientist in the Sinclair lab, had been studying mice in which this SIRT1 gene had been removed. While they accurately predicted that these mice would show signs of aging, including mitochondrial dysfunction, the researchers were surprised to find that most mitochondrial proteins coming from the cell's nucleus were at normal levels; only those encoded by the mitochondrial genome were reduced.

"This was at odds with what the literature suggested," said Gomes.

As Gomes and her colleagues investigated potential causes for this, they discovered an intricate cascade of events that begins with a chemical called NAD and concludes with a key molecule that shuttles information and coordinates activities between the cell's nuclear genome and the mitochondrial genome. Cells stay healthy as long as coordination between the genomes remains fluid. SIRT1's role is intermediary, akin to a security guard; it assures that a meddlesome molecule called HIF-1 does not interfere with communication.

For reasons still unclear, as we age, levels of the initial chemical NAD decline. Without sufficient NAD, SIRT1 loses its ability to keep tabs on HIF-1. Levels of HIF-1 escalate and begin wreaking havoc on the otherwise smooth cross-genome communication. Over time, the research team found, this loss of communication reduces the cell's ability to make energy, and signs of aging and disease become apparent.

"This particular component of the aging process had never before been described," said Gomes.

While the breakdown of this process causes a rapid decline in mitochondrial function, other signs of aging take longer to occur. Gomes found that by administering an endogenous compound that cells transform into NAD, she could repair the broken network and rapidly restore communication and mitochondrial function. If the compound was given early enough—prior to excessive mutation accumulation—within days, some aspects of the aging process could be reversed.

Cancer connection

Examining muscle from two-year-old mice that had been given the NAD-producing compound for just one week, the researchers looked for indicators of insulin resistance, inflammation and muscle wasting. In all three instances, tissue from the mice resembled that of six-month-old mice. In human years, this would be like a 60-year-old converting to a 20-year-old in these specific areas.

One particularly important aspect of this finding involves HIF-1. More than just an intrusive molecule that foils communication, HIF-1 normally switches on when the body is deprived of oxygen. Otherwise, it remains silent. Cancer, however, is known to activate and hijack HIF-1. Researchers have been investigating the precise role HIF-1 plays in cancer growth.

"It's certainly significant to find that a molecule that switches on in many cancers also switches on during aging," said Gomes. "We're starting to see now that the physiology of cancer is in certain ways similar to the physiology of aging. Perhaps this can explain why the greatest risk of cancer is age. "

"There's clearly much more work to be done here, but if these results stand, then many aspects of aging may be reversible if caught early," said Sinclair.

The researchers are now looking at the longer-term outcomes of the NAD-producing compound in mice and how it affects the mouse as a whole. They are also exploring whether the compound can be used to safely treat rare mitochondrial diseases or more common diseases such as Type 1 and Type 2 diabetes. Longer term, Sinclair plans to test if the compound will give mice a healthier, longer life.

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User comments

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foolspoo
4.7 / 5 (3) Dec 19, 2013
So youre saying henry ford didn't kill my dream and i will live to see the personal flying craft
Shakescene21
3.7 / 5 (6) Dec 19, 2013
Very good. A treatment that not only slows down ageing, but actually reverses some of the processes, and keeps us active and healthy longer. I hope this pans out -- soon.
AgnuTheInstigator
1.8 / 5 (5) Dec 19, 2013
Is it an entirely intelligent idea to encourage anti ageing when we cannot even figure out how to get the majority of the planet to the ripe age of 40?
Is it even a good idea to help people get to the age of 40 when as a society we cannot figure out how to move towards less polluting industries. The more people that live longer, the longer more people need employment.

The kicker- we can only provide them with opportunities that are disastrous for the environment unless we can figure out universal education and some sort of humanist approach to finance/wealth/nationality...

^My post is poorly written and leftist rambling but nonetheless- we should really examine all ramifications to the globe as a system. It is a very cool technological breakthrough and it may enable us to create a society where people like Feynman didn't have to die and could be sorting out problems like Warp Drives. But, it could also further hurt poorer nations and allow baddies like Hitler/Madoff to live forever
adam_russell_9615
5 / 5 (3) Dec 20, 2013
Where can i get some NAD?
zaxxon451
not rated yet Dec 20, 2013
Somehow I doubt the Fountain of Youth will be covered by medicare/medicaid. Our corporate owners need a disposable labor market, plenty of tax loopholes/havens, and free trade so they can find the cheapest slaves.
Sinister1812
not rated yet Dec 20, 2013
Some of us might be young, but we're not getting any younger.
David_Govett
5 / 5 (1) Dec 20, 2013
20-year-old mitochondria + 60-year-old vascular system = 911
big_hairy_jimbo
5 / 5 (1) Dec 22, 2013
I find this very interesting. Over the last few years we have started to learn how bacteria communicate with one another. We have even learned more about the human endocrine system by extrapolating bacterial communication to eukaryote multicellular communication. It seems that every cell in our body communicates in a similar way to individual bacteria. Even intestinal bacteria have been shown to release chemicals that communicate with our brain and vice versa. Now considering that mitochondria are considered to be an ancient bacterium that was engulfed by another bacteria, and that a symbiotic relationship between the two emerged giving an evolutionary advantage, I'm not surprised that a mitochondria and its host cell have signalling molecules. It would seem there are huge advances to be made by studying bacterial and cellular communications. The human is a whole organism made from multiple separate organisms all communicating. We are advanced jellyfish!!
EnricM
not rated yet Dec 23, 2013
^My post is poorly written and leftist rambling but nonetheless- we should really examine all ramifications to the globe as a system.


you are absolutely right.
The main problem that we face today is not aging or disease, not even AGW or polution, it's overpopulation.

I don't share a leftist point of view and I don't even see such advances as the one described as improvements until we can adress the issue of the planetary resources (including environmental resources, of course)
Whydening Gyre
5 / 5 (1) Dec 25, 2013
Where can i get some NAD?

Don't you already have it?
Go-NAD's...
Melissa Willow
1 / 5 (1) Jan 09, 2014
I found a company selling a supplement containing NAD (www.zaoreset.com) and am thinking of trying it. Has anyone else tried this product yet?
Whydening Gyre
1 / 5 (1) Jan 09, 2014
I found a company selling a supplement containing NAD (http://www.zaoreset.com) and am thinking of trying it. Has anyone else tried this product yet?

I never "1" any commenters on Phys.org - unless they are just trying to sell something.