The biology of ageing

Rod Long, Coum Unsplash

At the fourth International Australian Biology of Ageing Conference 2019, world-renowned luminaries reinforced the premise that eating less is the primary way to slow down ageing. We’ve actually known this for quite a while. The buzz phrase is “caloric restriction” and it comes in many guises. You can try alternate day fasting or the much easier gambit of simply eating a mere 10 per cent less at each meal. And then there’s the much-vaunted 5/2 diet whereby you gorge yourself into oblivion for five days and spend the other two hunkered down in a 500-calorie restricted bunker.

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The problem with any of these diets is sustaining them for an extended length of time. As Stephen Simpson, professor in the aptly titled School of Life and Environmental Science at the University of Sydney, was at pains to explain, besides the fact that we love to eat and don’t endure persistent hunger very well, we are compelled by what is called “the protein leverage hypothesis”, a biological drive to eat protein regularly and often to survive. Aside from our need to eat protein, what is also subverting our longevity strivings is our constant immersion in a bottomless well of highly palatable foods that are oozing fat and sugar cleverly engineered to stoke an endless desire to consume. While the experts were nowhere closer to explaining how we could overcome these obstacles to starve ourselves for the long haul, what Professor Simpson did do was elaborate on what it is we could eat to live longer and healthier.

The diet

Ironically, we have to partially ignore the “protein leverage hypothesis” and eat less protein and more carbohydrates. Apparently, the more protein you ingest, especially that which is animal-based, the more you turn on an ageing- and disease-stimulating compound called mTOR. Professor Simpson advises that your protein sources should mostly be plant-based and that specifically you should steer away from chicken, turkey, cheese and eggs. He’s even constructed a food pyramid at whose base sit the carbohydrates, which is not pasta, bread and cereal but fibre-rich vegetables including cauliflower, sweet potato, Brussels sprouts, asparagus, cucumbers, squash and celery alongside fruits like berries, tomatoes, apples and oranges. Placed above these reside the grains, then on the next level are the beans, chickpeas, seeds and lentils flanked by the leafy green vegetables: spinach, broccoli, kale and lettuce. Finally at the apex we find the fats and oils comprising almonds, pecans, walnuts, avocado and olive oil.

The drugs and nutrients

For those who balk at the thought of changing their diet for any extended period of time to inhibit mTOR there are always pills we can pop to achieve the same effects.

Metformin

Metformin is a drug that has been used for eons to treat diabetics. It can also inhibit the growth of cancer cells, reduce blood sugar levels and quell inflammation, all longevity promoters, allowing this drug to extend the lifespan of worms and mice, but long-term trials demonstrating anti-ageing benefits for humans have just began. Metformin doesn’t come without a downside. It can lower vitamin B12 levels, an important brain-protecting nutrient, thereby raising homocysteine, a protein that is usually kept in check by adequate amounts of vitamin B12, the consequence possibly increasing the risk of Alzheimer’s according to limited evidence. Most research however does show that metformin protects against Alzheimer’s, probably because some of the benefits listed above. Nausea is probably its most immediate disadvantage, and with other gastro-intestinal side effects it might not be the most attractive option.

Rapamycin

This is another drug that received a lot of airtime at the conference. Used as an immune suppressant after kidney transplantation it also has longevity potential, and aside from extending the lifespan of yeasts, worms, fruit flies and mice it might also prevent heart disease, osteoporosis, Alzheimer’s and Parkinson’s disease. Such a monumental benefit doesn’t come without a deleterious price tag including diarrhoea, raised blood-sugar levels, mouth ulcers and pneumonia, making this pharmaceutical even more off limits than metformin.

All of these medicinal complications have driven the search to find natural mTOR inhibitors without side effect baggage.

Herb-based compounds

Top of this list is withaferin-A, a compound that comes from the same family from which Withania somnifera, a herb that boosts adrenal function, is derived. Based on experiments carried out in the test tube and on mice, it has antioxidant and anti-inflammatory capabilities with anti-diabetic, anti-obesity and anticancer properties. Other candidates with similar advantages include allantoin, one of the active compounds mediating the beneficial effects of yam and the well-known herb ginseng. While compared with rapamycin and metformin their lack of side effects makes them highly appealing, what we don’t have is the human evidence proving these natural substances actually enhance longevity.

Senolytics

Another easier longevity choice proffered by the experts for those who shirk persistent dietary adjustments are senolytics, remedies that nuke age-fomenting senescent cells.

Found in apples, grapes, persimmons, strawberries, cucumbers and onions, fisetin is the most powerful natural senolytic, quashing cancer cells and encouraging other ageing cells to self-immolate and make way for more youthful actors.

Quercetin is another senolytic present in apples, onions, tea and red wine.