Pomegranates, turmeric and red grapes: the key to long life? | Life...

https://www.theguardian.com/lifeandstyle/2016/oct/10/pomegrana...

Pomegranates, turmeric and red grapes: the

key to long life?
Cells keep the body healthy by devouring toxic waste to fight off everything from
wrinkles to dementia. Could certain foods help?
Ann Robinson
Monday 10 October 2016 07.30BST

utophagy literally means self-devouring something our cells are doing

constantly, breaking down damage and toxic waste products and Japanese cell
biologist Yoshinori Ohsumi has just been awarded the Nobel prize in medicine
for his work in uncovering the complex mechanisms that underpin this
remarkable internal recycling system. So how does autophagy keep us healthy? Why
might dysfunctional autophagy contribute to diabetes, dementia, leukaemia and
Parkinsons disease? And will our new understanding lead to any cures?
The process of autophagy involves gathering up cellular junk and waste, sealing it in the
cellular equivalent of a bin bag and transporting it to the cellular rubbish bin, called the
lysosome, where enzymes break down the contents. I often call autophagy the
recycling van that delivers the rubbish to the recycling centre, says Professor Katja
Simon, of the Kennedy Institute of Rheumatology in Oxford. It plays a key role in health,
disease and ageing, she says: It is very important to degrade toxic waste for the survival
of the cell, and a cell without autophagy cannot survive. But it has also been shown that
it is important in disease development, such as in Parkinsons disease, which is
characterised by the accumulation of protein aggregates in neuronal cells. Furthermore,
autophagy levels fall in the ageing process. The characteristics of old age, such as
wrinkles, hearing loss or cancer, are actually due to falling autophagy levels and the
accumulation of toxic wastes in the cells.
Simons work is particularly focused on red and white blood cells and disorders such as
leukaemia, in which autophagy doesnt work properly. She is delighted that Ohsumi has
been awarded the Nobel prize. In the 1960s, he used an electron microscope to see
structures and no one knew what they were. He discovered the molecules involved in
the process. Ohsumis lab mainly works with yeasts, and has uncovered key genes
involved in autophagy. The science has come a long way since the 60s and researchers
such as Simon can now measure autophagy by tracking the ow of labelled molecules
associated with the process.
Mopping up damaged mitochondria the powerhouses of cells that release energy
seems to be especially important in preventing diabetes and obesity. When this
particular form of autophagy, called mitophagy, doesnt work properly, toxic chemicals
build up that cause further mitochondrial damage. This vicious cycle damages cells in
the pancreas that produce insulin, and diabetes can set in. A drug that can x diabetes

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and obesity by sorting out disordered mitophagy is an attractive idea, but were not there
yet.
Another key role of autophagy is found in its link in proteins. In the body proteins are
folded into 3D shapes. Aberrant proteins that arent folded up properly can form large
clumps, or protein aggregates, that can be cleared by autophagy. When autophagy fails,
the aggregates damage nerve function. This process is thought to contribute to the
changes seen in Parkinsons disease, including tremors, slow and sti movement, loss of
smell and dizziness. The abnormal accumulation of proteins in the brain may be the
common thread in dierent forms of dementia that cause debilitating loss of memory,
language, judgment and cognitive and social functioning.
If scientists can stimulate autophagy, they could eectively stave o or even reverse the
eects of ageing. As Simon says, its not about making people live for ever, but about
nding ways to stay healthy as we live out our lives. Studies on mice have found that
stimulation of autophagy removes accumulated misfolded proteins, broken
mitochondria and damaged DNA in hearts with age-related changes. But translating this
lab work into eective treatments for humans is still a way o.
Autophagy declines during ageing and this has a major impact in our cells, since they
accumulate toxic deposits, says Ioannis Nezis, an associate professor at the University
of Warwick. This is especially harmful for neurons, since neurons do not divide, and
the same cell keeps accumulating garbage. If we understand how autophagy is normally
induced to selectively recognise and recycle these toxic deposits, we will be able to nd
compounds that can activate autophagy and keep its levels steady during the course of a
lifetime and therefore avoid the accumulation of cellular garbage. These can be chemical
drugs, or natural dietary compounds that can be used as supplements.
So what can we eat to keep us autophaging eciently? Nezis says lots of natural
compounds have been tested in fruit ies, mice and test tubes, but we still dont know
for certain what works in humans and what amounts are needed. Pomegranates,
turmeric, red grapes and red wine look hopeful, but Nezis says you may need litres of
wine and kilos of grapes to get the required eect. Supplements containing distilled
concentrates of the active molecules may prove more palatable.
Simon points out that cells switch on autophagy in response to starvation. Calorie
restriction, such as intermittent fasting in the 5:2 diet or during Ramadan, may help us
to live long and healthy lives. It is possible that reducing our calorie intake to 70% of
what we have been used to eating will boost our autophagy and help to prevent a wide
range of disease. Exercise also promotes more autophagy, as experiments that get mice
to run on mini treadmills has shown.
Advice to feast on fruit, veg and red wine is hardly new. But thanks to this years Nobel
prize-winner, our understanding of the science that underpins it is developing all the
time. The next step will be drugs, supplements and interventions that could stave o the
ravages of ageing and a host of debilitating diseases. We are not there yet, but we are one
step closer.
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