Groundbreaking Study Suggests a Way to Reverse Ageing
Scientists from the National Institute on Aging, and the University of New South Wales, Sydney, Australia, Harvard Medical School have discovered a cause of ageing that fortunately, can be reversed.
By administering a molecule naturally produced by the body, the research team were able to restore the communication network in older mice, which resulted to significant benefits comparable to that of younger mice. "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 David Sinclair, senior author of the study and Professor of Genetics at Harvard Medical School.
Researchers have generally been doubtful of the idea that ageing can be reversed due mainly to the prevailing theory that age-related illnesses are the result of mutations in mitochondrial DNA, and that mutations cannot be reversed.
Mitochondria are referred to as the cell’s ‘powerhouse’ – the area where chemical energy is generated that carries out essential biological functions. These self-contained organelles, found in the centre of the cells, have long been identified as key biological players in ageing. Previous studies have shown that as mitochondria become increasingly dysfunctional over time, many age-related conditions such as Alzheimer’s disease and diabetes gradually set in.
Sinclair and colleagues have been studying the fundamental science of ageing, focusing primarily on a group of genes called ‘sirtuins’. Past research has shown that one of these genes, called SIRT1, was activated by resveratrol, a compound present in grapes, red wine and certain nuts.
In one lab experiment, the research team examined mice whose SIRT1 genes have been removed. Whilst they accurately predicted that the mice would demonstrate signs of ageing, including mitochondrial dysfunction, they were surprised to find that most mitochondrial proteins coming from the cell’s nucleus were at normal levels. Rather, only those encoded by the mitochondrial genome were reduced.
By investigating further, researchers found that a 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.
However, for reasons still unclear, the levels of NAD in the body decline as a person advances in age. And 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. The researchers found that this loss of communication reduces the cell’s ability to make energy, and signs of aging and disease become apparent.
Ana Gomes, a postdoctoral scientist in the Sinclair lab, 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.
After administering the NAD-producing compound for just one week, the researchers examined samples of muscle tissue in two year-old mice and looked for indicators insulin resistance, inflammation and muscle wasting. In human years, this would be like a 60-year-old converting to a 20-year-old in these specific areas.
Another groundbreaking finding was about the HIF-1. Normally, it is activated when the body is deprived of oxygen. Otherwise, it remains silent. Cancer, however, is known to activate and hijack HIF-1.
"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," explained Sinclair.
The team is now investigating whether the NAD-producing compound can be used to safely treat rare mitochondrial diseases or more common diseases such as Type 1 and Type 2 diabetes, and whether it can be used to promote longer, healthier lives.
Their findings were published in the journal Cell.
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