Published 7 June 2023 by Arunima Roy

In Search of Youthfulness: An Unhelpful Guide to Longevity from a Skeptic

People are trying to stop the process of ageing. Photo/Credit: Petrovich9/iStockphoto.

Early career scientists prefer to look their age. After all, and I speak from experience, a lack of grey hairs can be counted against you in the tenure race. Others usually are not too keen on getting old. And it seems beating ageing, both the desire and the ability to do so, is heavily correlated with one’s net worth. Billionaire Bryan Johnson for instance, spends two million a year to stay young. He claims to have de-aged five years in seven months. With any luck, he’ll to return to an embryonic state in about six years.

If you daydream of what to spend your millions on, here’s some ideas. A popular way to extend your lifespan is by microdosing on LSD. Sounds fun? Let’s not trip over with excitement, for I suspect it is bad in the long run. Or you can try a fecal transplant from a younger person, which is exactly what you are imagining it to be like, except that it is not supposed to be DIY, but needs specialised doctors. And if this isn’t to your taste, don’t be disheartened. There are other anti-ageing options, like young blood transfusions, which also explains how vampires outlive us.

Some proponents of these anti-aging (or biohacking) therapies hope to attain immortality. Others have more humble desires, such as improving health in old age. The latter is a respectable goal, but I am not interested if that involves locking myself in a hyperbaric chamber. Or applying the smoked toxic secretions of a giant monkey frog on open wounds (Kambo therapy). I am sure someone came up with that idea after microdosing on LSD.

The Answers of Research

It may seem obvious, but the only anti-ageing strategies consistently backed by research are healthy diets and exercise. Both are more difficult to commit to and consequently not as newsworthy. Calorie restriction and plant-based diets have a positive impact on health (note that calorie restriction has critics as well). Similarly, exercise delays chronic health problems and boosts longevity. High-intensity interval training and endurance training can be quite effective in this respect.

Healthy diets and exercise can modulate the four cellular nutrient-sensing pathways involving sirtuins, mTOR (mechanistic target of rapamycin), AMPK (5′adenosine monophosphate-activated protein kinase), and IGF-1/GF (Growth hormone/insulin-like growth factor-1). These pathways are responsible for reducing oxidative damage, maintaining genomic stability, and controlling cellular reproduction, all of which in turn affect ageing. Repeated calorie restriction and exercise, it is believed, activates these pathways to make our cells efficient in managing DNA damage. Exercise and calorie restriction can be thought of as a drill for our cells. They provide tiny bits of surmountable stress at the molecular level, which in turn improve the ability of our epigenes to repair DNA and prevent ageing (hormesis).

Molecule Resveratrol
Resveratrol. Photo/Credit: theasis/iStockphoto

It is hypothesised that any stressor that induces hormesis can increase longevity. However, experiments have failed to produce evidence in support. Cold exposure, believed to be such a stressor, is endorsed by celebrities, but has hardly any scientific backing. Next, resveratrol, a natural phenol found in grapes and berries, was believed to activate the sirtuin pathway, mimicking the effects of caloric restriction. Human studies though failed to find any such effects. Pfizer and Amgen reported that resveratrol had no effect on sirtuin activity and in 2010, GSK ended all resveratrol trials citing disappointing results. In fact, many researchers are now convinced that sirtuins do not affect ageing after all.

Successive Hypes on Molecules

Resveratrol went through the hype cycle a decade ago. Now another molecule is taking its place. NAD precursors, which include nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), are all the rage. NAD (Nicotinamide adenine dinucleotide) is essential for cellular function and the activity of those controversial sirtuins. NR and NMN are supposed to improve cellular NAD levels. Studies show positive effects of NMN and NR supplementation on yeast, worm, and mice lifespans. However, studies on humans are inconclusive. To some anti-ageing enthusiasts though, this is no deterrent, perhaps because rodents and invertebrates have a sufficient likeness to themselves. Online forums are replete with such pioneers self-titrating doses, and since there are no pharmacokinetic or toxicity studies, I wish them luck.

Collection of healthy greens like avocado, broccoli or salad
One piece of the puzzle for a healthy life is quite classic: Healthy food. Photo/Credit: KucherAV/iStockphoto

In the end, what we are left with is an appreciation of healthy diet and physical activity. These may slow down ageing and stall the onset of chronic diseases via their effects on cellular nutrient sensing pathways. For this article, I decided to alter my diet and experience first-hand the de-ageing effects of caloric restriction. After cutting out all animal-based foods (too much protein and bad for longevity), fats (poor cardiovascular health, shortens lifespan), and carbohydrates (also bad for longevity… need I repeat myself?), I was left with a bowl of unsalted greens and legumes for dinner. Unsurprisingly, my resolve failed in a week. I didn’t get any younger, but I developed an appreciation of ruminants.

It will take large studies, preferably in different populations, to assess anti-ageing interventions. Ethics aside, such a study will need to continue for a very long time to discern the intervention’s effects. Meanwhile, one wonders the point of such a study when there are plenty of other pressing problems.

An Honest Conclusion

Preventing chronic disease is important, but extending lifespans is not. Assuming fertility rates stay the same, an increase in population size from living longer will only add to resource scarcity. If current population levels are to be maintained, then the proportion of younger individuals will reduce. A younger population is, however, essential to maintain productivity and generate new ideas. Moreover, any life extension methods, at least initially, will be expensive and accessible to only the very wealthy.

For those who argue lifespan extensions will truly allow us to fulfill our potentials, here’s sage advice from someone who struggled to write a thesis: if you cannot complete something in the allotted time, an extension will be of little use.

The content of the article reflects solely the opinion of the author.

Arunima Roy

#LINO18 Alumna Arunima Roy works in public health as an analyst. She previously studied the effects of environment on mental health disorders, including attention-deficit/hyperactivity disorder (ADHD). When not at work, she will be either playing computer games or trying her hand at writing fiction. She is passionate about science communication and hopes one day to parent two dogs whom she will name ‘Crispr’ and ‘Cas’.