Making Our Way Towards Eternity

On January 8, 2003, the eyes of the world were on the death of a mouse. No, I’m not talking about Stuart Little, I’m actually speaking about a laboratory mouse who lived 1819 days – almost 5 years1. That means this mouse, named GHR-KO 11C lived almost twice the average life span. Since then, numerous lab mice have passed their fourth birthday, which resulted in the discovery of five genes, two diets, and five drugs that expand their lifespan. But there’s an animal that clearly takes the prize home – Hydra vulgaris. This little dude left the scientists perplexed when they found out he may as well be potentially immortal1.

But how come some animals outlive others? Aristotle thought it had to do with moisture2.  In the last few years, it was hypothesized animals with higher metabolic rates live shorter lives, but that doesn’t really add up since parrots, whose hearts beat up to 600 times per minute, outlive other animals with slower metabolic rates. Actually, the only thing we know so far is that bigger animals usually live longer than smaller ones2. We think that happens because they have fewer predators. No one is going to bother elephants or whales, so they can invest their resources in building stronger immune systems and producing offspring. On the other hand, rats and other small animals spend their life in ‘fast-forward’, always fleeing from predators and avoiding environmental pressures.

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The thing is: we don’t understand ageing. We are not even close to doing so. And if we don’t understand it, we can’t stop it. If you somehow got a blood sample from someone, you couldn’t really tell what the age of that person was, since we don’t have any reliable markers linked to aging. The molecular changes that happen with ageing suffer considerable variations from one individual to another, making them unreliable to determine someone’s age. It was precisely that problem that destroyed the initial hype about telomeres. Telomeres, as you probably have heard, are protective caps on the ends of chromosomes that become a little shorter every time the cell divides. If the length is too small, the cells stop dividing. We initially thought they were the aging biomarkers we so much needed, but, unfortunately, there is a lot of diversity of length between people of the same age. We found ways to extend the size of telomeres and, therefore, increase our lifespan, but that comes with a heavy cost: an increased risk of developing cancer. It turns out our cells stop dividing to prevent themselves from developing cancer3.

There’s a coenzyme found in all living organisms that seems to hold promise for stopping aging. Its name? Nicotinamide adenine dinucleotide. But let’s call it by its street name – NAD+. Cellular NAD+ concentrations change throughout our life and we can potentially modulate them to bring aging to a halt4. Supplementation with NAD+ precursors seems to not only prolong  the health span and the life span, but also protect against neurodegenerative diseases. Unfortunately, it also increases the probability of developing immune diseases and tumors4. Mitochondria – the so-called powerhouse of the cell – was also on the spotlight some time ago. Everyone thought it was one of the major causes of ageing, since it produces toxic reactive oxygen species, however the age-dependent mitochondrial dysfunction does not seem to be sufficient to reduce life span5. Recently, even gut microbiota was involved. It seems that the bacterial diversity in our gut is lost as we age, making some people more prone to the aging-related health loss6. Dietary restriction has also been one of the most studied areas in gerontology, since it was shown that it can increase life span in some populations7. The problem with dietary restriction is that it can’t be implemented to the whole population, which is making researchers look into alternatives, such as low-protein diets7.

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No single marker is likely to give a definitive reading of a person’s true age.  As you can see, there are a lot of molecules and biological markers which are currently being studied to see whether they are or not associated with ageing. And when there is a multitude of hypotheses involved, it’s because we have no idea what’s really happening. Our knowledge about aging is, at the very least, fragmentary, but Science is making its way toward a three-digit life span.

Sources:

1 – Cohen, Jon. “Death–defying experiments.” Science 350.6265 (2015): 1186-1187.

2 – Grimm, David. “Why we outlive our pets.” Science 350.6265 (2015): 1182-1185.

3 – Underwood, Emily. “The final countdown.” Science 350.6265 (2015): 1188-1190.

4 – Verdin, Eric. “NAD+ in aging, metabolism, and neurodegeneration.” Science350.6265 (2015): 1208-1213.

5 – Wang, Ying, and Siegfried Hekimi. “Mitochondrial dysfunction and longevity in animals: Untangling the knot.” Science 350.6265 (2015): 1204-1207.

6 – O’Toole, Paul W., and Ian B. Jeffery. “Gut microbiota and aging.” Science350.6265 (2015): 1214-1215.

7 – Kaeberlein, Matt, Peter S. Rabinovitch, and George M. Martin. “Healthy aging: The ultimate preventative medicine.” Science 350.6265 (2015): 1191-1193.

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