Bristlecone pine.

Since ancient times, people have been searching for the fountain of youth. While no one has quite found it yet, life expectancy has steadily increased. Over the past 200 years, human life expectancy has more than doubled thanks to better nutrition, improved safety and advances in medicine.

Still, there does seem to be a limit to how old humans could grow to be. In 2016, a very high profile study published in Nature argued that humans have a maximum lifespan of around 115 years. But does that limit have to exist or can it be shattered?

Well, if you look at nature, there are some living things that seem to be able to live forever, or at least for a very long time. Bristlecone pine trees are more or less biologically immortal. Scientists have examined some 5,000 year-old Bristlecone trees and have found their vascular tissues functioning just as well as in young trees. A study published in 2001 compared pollen and seeds from bristlecone pines of various ages up to 4700 years, and found no significant increase in mutation rates with age.

Some sea creatures, such as the Hydra (Hydra viridissima), seems to not age biologically at all. These tiny soft-bodied creatures are only about 15mm in length and they carry stem cells that are so potent that they can regrow significant chunks of their own bodies if it gets damaged or injured (which explains how it got its name, based on the mythological Hydra which can regrow its head when chopped off).

Seeing such phenomenon in nature has given some people motivation to find ways to prevent or at least reduce decay in the human body.

WARDING OFF OLD AGE


Juan Carlos Izpisua Belmonte.

One promising approach involves metformin, a common diabetes drug. Studies on animals have suggested that it could protect against frailty, Alzheimer’s and even cancer, among other things. Metformin is part of a broader category of drugs called mTOR inhibitors which interfere with a cell protein involved in division and growth. It’s believed that lowering the protein’s activity mimics the well-known benefits of calorie restriction diets which have been shown to help animals live longer.

Nir Barzilai, the founding director of the Institute for Ageing Research, is leading a human trial called TAME (Targeting Aging with Metformin) that aims to administer it to people aged between 65 and 80 to see if it is able to ward off diseases associated with old age such as cancer, dementia, stroke and heart attacks. He plans to start testing on recruits later this year.

Another approach involves epigenetics. Juan Carlos Izpisua Belmonte of the Gene Expression Laboratory at San Diego’s Salk Institute for Biological Studies has managed to rejuvenate mice suffering from old age illness.

He has done extensive experiments on mice which have progeria, a disease caused by genetic mutation that accelerates ageing. Mice with progeria that are only three months old would have organs that are failing and appear to be on the verge of death. But once fed with an age-reversal mixture, they get rejuvenated and become lively and active. Unfortunately, the treatment is so potent that it actually kills them after just a few days. Many of them die due to tumours that they develop.

Epigenetic marks are chemical groups that wrap around a cell’s DNA and function as a kind of on/off switch for genes. Over time, the accumulation of changes in our cells causes them to function less efficiently, which is why we age. What Izpisua Belmonte and his team have done with the mice is reset their bodies’ epigenetic marks. Once the marks are erased, their cells would revert to a more primitive, embryonic state.

Izpisua Belmonte believes that epigenetic reprogramming may be the fountain of youth that we’re looking for. Well, not exactly. It can’t help you live forever but Izpisua Belmonte believes it could significantly delay your death.

IMPROVING LONGEVITY


Hydra.

The treatment he gave his mice is based on a Nobel Prize-winning discovery by noted Japanese stem-cell scientist Shinya Yamanaka, who in 2006 demonstrated how adding just four proteins to human adult cells could re-programme them so that they look and act like those in a newly formed embryo. These proteins, called the Yamanaka factors, help clean the epigenetic marks in a cell.

Theoretically, if applied to humans, you could also rejuvenate their bodies by clearing their epigenetic marks. But there are dangers involved. Mice with progeria that underwent cellular reprogramming ended up getting tumours, which ultimately proved fatal.

Izpisua Belmonte believes there could be a way to give the mice a less lethal dose of reprogramming. But even so, that doesn’t mean the effect he saw on mice that had progeria would also happen with humans. In tests on normal mice – with the progeria disease but which were elderly – he wasn’t able to get the same results.

That’s probably because unlike progeria, which is due to a single DNA mutation, ageing is a much more complex issue. Perhaps someday they will find a way to make this rejuvenation work safely for humans but it seems to still be a long way off.

In the meantime, perhaps the best way to improve longevity is to eat sensibly, avoid carcinogen, and get regular exercise. Even if you can’t significantly extend your lifespan this way, at least you’d be able to improve your “health span”, which refers to how long you can stay healthy and functional.

Oon Yeoh is a consultant with experiences in print, online and mobile media. Reach him at [email protected].

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