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In April 2017 the world’s oldest living woman – Emma Morano – died at the age of 117. According to official records this makes her the fifth oldest person to ever have lived. The oldest recorded person, Jeanne Calment, lived to an astounding age of 122 years.  Morano attributed her long lifespan to both her genes and the eggs which she ate at least three times a day, two of them raw. Calment instead was reported to have smoked until she was 117, consumed large amounts of chocolate, and credited olive oil for her longevity.

Regardless of the reasons, Morano and Calment are rare – even living to 100 is enough to warrant a message from the Queen for centenarians living in the UK. However, with the rapid advance of technology and modern medicine the number of people becoming centenarians or even supercentenarians (living past 110) is increasing, with the United Nations predicting that we will see nine times as many people living for over a century by 2050.

 

Measuring the aging process

As our potential to reach older ages increases, it becomes imperative that we understand how aging affects our bodies, and the best ways to manage it.

As our potential to reach older ages increases, it becomes imperative that we understand how aging affects our bodies, and the best ways to manage it. As an expert in geroscience – a field that investigates the relationship between aging and age-related diseases – Simon Melov, from the Buck Institute for Research on Aging, has reviewed some of the popular metrics and models which are used to study aging in mice and invertebrates, and has proposed how this can be applied to preclinical studies.

Movement speed is one of the simplest to measure, and is known to correlate with an increased lifespan. Whilst we mostly do it without thinking, it actually encompasses a wide variety of mechanisms including balance, strength, coordination, and cognitive function. We also have such a wide range of activity trackers and step counters available – chances are you’ve at least one on your person right now. Our walking speed is now a very simple metric to measure and track.

 

Quantity vs Quality of Life

As age increases, age-related diseases also become more probable.

Melov makes a distinction between lifespan and healthspan in his review, and it’s an important distinction to remember – as age increases, age-related diseases also become more probable. For example, in a study recently published in F1000Research, Brian Diffey and Steven Frank observed that historically, the incidence of malignant melanoma increases as people get older. They analysed almost 40 years of data from Australia, Great Britain, and the USA (areas with very different levels of sunlight) to investigate whether the relationship between age and malignant melanoma is changing.

Across all countries, genders, and the years in which people were born there was a clear trend in the increase of melanoma incidences as people got older – however, for some groups this occurs faster than others. The rate of increase appears much higher for males when compared to females, especially males from Great Britain, and slower for Australian females.

It is heartening to note that in recent years, whilst the incidence of malignant melanoma is increasing overall, the relationship between this and age is less prominent across all the groups observed. As Robert Noble mentions in his peer review report for the first version of this article, this could be due to a number of factors ranging from an increase in screening, examinations, and general medical knowledge, to simply changes in fashion and culture.

 

The aging brain

It can be difficult to separate out the natural effects of age from the effects of age-related pathophysiological disorders

As well as the physical impact of growing older, we must also bear in mind the effect of aging upon the brain. Part of the problem when studying this is that it can be difficult to separate out the natural effects of age from the effects of age-related pathophysiological disorders, as discussed in Zachariah Reagh and Michael Yassa’s recent review.

They explain that as we age our synapses and axons degenerate, which can result in memory loss. Interestingly, these dysfunctions do not occur uniformly across the brain – as mammals age areas of the hippocampus, which is associated with memory, have been found to be hyperactive whilst the prefrontal cortex, a part of the brain related to executive function and cognitive planning, displays greater inhibition. These could contribute to memory loss and reduced cognitive function, some of the early symptoms of Alzheimer’s disease.

Sam Gandy and colleagues note that currently, we are facing major difficulties in fighting Alzheimer’s disease. Whilst there are treatments to help alleviate the symptoms, we have yet to find an effective disease-modifying drug, despite billions of dollars being invested.

Gandy and colleagues propose that the lack of success so far is because we are not targeting Alzheimer’s disease at the preclinical stage. They also emphasise that there are still many gaps in our knowledge of Alzheimer’s disease and that we should remain open-minded, investigating new models such as canine cognitive dysfunction and considering the possibility of other pathways than the traditional focus on clearing plaques caused by protein clusters.

 

Pushing the boundaries

Even once we can manage age-related diseases more effectively, the question remains – how long can we actually live for?

Even once we can manage age-related diseases more effectively, the question remains – how long can we actually live for? Whilst some researchers focus on methods with which we could extend and improve our lifespans, Xiao Dong and colleagues instead investigated in their Nature paper whether there is a limit to how far we can increase human longevity, using data provided by the Human Mortality Database, the Gerontological Research Group, and the International Database on Longevity.

Their analysis – which investigated the lifespans of people from Japan, France, UK and USA – determined that our maximum potential lifespan is beginning to plateau despite the progress of medical science, and they predict that the longest a human could live is to 125 years (with the possibility of someone exceeding this being less than 0.01%). Dong et al. propose that this is a natural limit, a safeguard against genetic errors introduced throughout our lifetime.

However, recently Saul Newman and Simon Easteal reanalysed the same sets of data, and came to a more optimistic conclusion. Not only did they find that 130 years would be a more likely limit to the human lifespan, but in contrast to Dong et al. they observed no plateau of our maximum potential age. Instead, they report that the human lifespan is continuing to increase.

The human lifespan is continuing to increase.

Whilst often experiments are replicated (or not replicated, as the case may be) it is perhaps less common for two analyses of the same data to demonstrate such conflicting trends – in part, Newman and Easteal attribute these differences to errors in the original calculations of Dong et al. However, they also note that some of the observed trends could be related to how the data is reported and collected, limitations which were not mentioned in the original study.

Importantly, the International Database on Longevity stopped collecting data from France and the USA after 2003. Considering that over 60% of living verified supercentenarians were from these countries in 2007, it is likely that their exclusion from the data has had an impact on the apparent trends in maximum observed lifespan. When data from the four countries is analysed separately, the plateau observed by Dong et al. is no longer present. This means that rather than the 125 lifespan limit originally suggested, it is possible that our maximum age could continue to increase much further. However, as noted in the peer review from Jean-Michel Gaillard, the lack of plateau could in part be because Calment was removed from the re-analysis as an anomaly – whilst her longevity could indeed be considered anomalous, she is the only verified person to have reached such an age since her death 20 years ago. Counter to Newman and Easteal’s hypothesis, rather than Calment being an outlier she could instead lend credence to the existence of a lifespan plateau.

Regardless of the specifics, whilst we don’t yet know all the factors that influence longevity – whether it’s olive oil, chocolate, or simply good genes – it seems it won’t be too long before Morano and Calment are joined by many other supercentenarians, and perhaps even surpassing their record-breaking lifespans.