In The Curious Case of Benjamin Button, a boy was born old and got younger. That film is science fiction but Australian scientist Professor David Sinclair, currently at Harvard University Medical School and his colleagues have managed to get yeast and more recently mice to grow younger.
Ageing has multiple causes, until recently none have been considered treatable. It is the diseases of old age: dementia, heart disease and osteoporosis that have been treated.
Research has led to lifespans increasing, but older people often spend years in poor health.
Humans have around 20,000 genes. These provide the cell with instruction to make proteins. Not all of them are needed in every cell. Those that aren’t needed are turned off by process called epigenetics. This ensures genes are not active in inappropriate cell types. For example the COL1A1 gene codes to produce collagen, but only needs to be active in skin, cartilage and similar types of cell.
Sinclair’s team believes that the loss of epigenetic information is the root cause of ageing. They have identified drugs that can reset a cell’s epigenetic status and reverse its age. These drugs can be delivered by a harmless virus to specific tissues or the entire body, thereby causing cells to act younger and wounds to heal faster.
Genes called sirtuins make enzymes that control how cells function and they can be used to turn off genes that hasten ageing.
Sever calorie restriction increases the lifespan of mice and yeast, but that’s not really practical for humans.
However, Professor Sinclair says a short period of being hungry or stressed in other ways causes sirtuins to turn on the mechanism that repairs cell damage and resets the biological clock.
Other compounds can activate sirtuins. Resveratol, found in small amounts in red wine, activates sirtuins in mice when fed large doses. Metformin, used to control blood sugar levels in diabetics, acts in the same way. Diabetics who take metformin tend to outlive those who don’t.
Next Sinclair’s lab looked at the way mitochondria (the cell organelles that generate energy) operate. The levels of nicotinamide adenine dinucleotide (NAD+) in mitochondria dictate how long cell survive, but NAD+ declines with age.
Professor Sinclair and his co-researchers found that restoring NAD+ levels in mammals has a dramatically positive effect on the liver, heart, reproductive organs, kidney, muscles, and brain and nervous systems. Old mice given a NAD+ booster drug ran around like young mice within a few days.
They study the mechanisms by which the NAD+ level repairs DNA and look for ways to improve this process. In particular, they study enzymes that deplete or increase NAD+ as potential tools to control the NAD+ level in the cells.
They have also actively looked for sirtuin activating compounds (STACs) and have discovered potent activators that raise NAD+ levels. They are testing these for their effects on ageing and age-related diseases.
But mice are not people, so it is too early to start taking NAD-boosting drugs until the results of human trials are completed.
Sinclair’s advice for longevity is to avoid scans and X-rays as much as possible as they damage your DNA and get a little bit hungry from time to time. He spends four hours a week at the gym, include one hour doing yoga and an hour in the sauna.
He says the stress of jumping into cold water after the hot steam room and hot tub increases brown fat in his body. Brown fat has lots of mitochondria which raises the metabolic rate and helps to prevent excessive weight gain.
