A 19 year old Turkish woman with liver disease was in urgent need of a liver transplant, and while on the waiting list she developed hepatic encephalopathy which caused her liver to start to shut down completely and doctors rushed to save her life.
The woman was running out of time, and the only option for her was a liver that had previously been turned down by other hospitals as it was considered to be in bad shape because it contained a cyst that was caused by parasitic infections, and came from a recently deceased 93 year old woman making it old by transplant standards for such as young recipient.
However, with no other organs available and little other choice, the transplant was performed at the Liver Transplant Institute at Inonu University in Malatya, Turkey in 2008. The procedure was a success with the young woman since then going on to give birth to a healthy baby girl, and on her daughter’s first birthday the woman herself had just turned 26 years old and had also just celebrated her liver’s one hundredth birthday.
While few of us will ever know what it is like to have an organ that is as old as an centenarian, remarkably some of our organs do have the capacity to actually outlive us while others age more rapidly; and the way that organs/tissues age could tell us more about how old our bodies are than counting numerical birthdays will.
Accumulating research is increasingly suggesting that our actual age appears to be far less important than one thinks, with there tending to be a discrepancy between chronological age and biological age. While these two numbers may be linked, they do not always match up, particularly when a lifetime of unhealthy eating, being sedentary, un-managed stress, and lack of sleep will without question age us prematurely.
Research suggests that there is a complex mix of genetic, lifestyle and environmental factors that combine to determine how quickly the body will age, but this does not affect all of the organs in equal measure. A person could appear to be 38 years old, but that same person could have the kidneys with the appearance of a 61 year old, as one study found. Just as one could in appearance have all of the hair loss and wrinkles of an 80 year old but still be maintaining the breathing heart equivalent to that of a 40 year old.
“Over time, the whole functioning of a car declines, but some parts wear out faster than others,” he says. “If your engine is starting to go you can fix that – if later the body wears out you can fix that, and so on,” says Michael Snyder who is a geneticist at Stanford University.
Transplant data from the University of Liverpool, UK is suggesting some clues as to which organs may fare better with age, however, there were significant differences depending on the organ in the study comparing the age of donors with factors such as how long the recipients lived post surgery finding that across the broad transplants tend to be less successful with older organs. The success rate with hearts and pancreases worsened after the age of 40, no age related differences were found with transplanted lungs until the donors were 65, and the corenas were found to be the most resistant organ with donor age appearing to have little effect.
The relative complexity of the organ along with their reliance on blood vessels to function may be factors in how they cope with age, with the researchers noting that: “It is logical to think that age-related changes in vasculature and microvasculature of the different organs must be a significant factor contributing to their age-related dysfunction.”
Their data raises questions of whether there is an upper limit on the lifespan of certain organs. Take for instance the liver is known for its regenerative capabilities, and some people with as much as two thirds of their livers removed have experienced the organ regrowing to its previous size within a year. Nonagenarians may well be an untapped pool of potential liver donors according to research and several successful transplants in recent years, with a group of transplant patients being monitored who’s livers have turned 100 several decades before the patients will.
Certain organs may be more sensitive to some aspects of our lifestyle than others. “A very good example is the lungs and pollution,” says Richard Siow, director of ageing research at King’s College London. “Lungs are more aged in the city, or in high pollution environments.”
“What we eat and how we eat it, how we sleep and when we sleep – all these things can impact our organs in varying ways that we don’t fully understand,” says Siow.
The concept of an organ age gets more blurred at the microscopic level, with the individual cells making up the organ wearing out and requiring replacement on a fairly regular basis, meaning that many tissues regenerate over time with the rate at which they do so varying widely. Most neurons are not replaced as we age, while red blood cells will circulate for on average 4 months, and cells in the gut needing replacing after only a few days. Neurons are not the only cells with a long lifespan, cells within the liver and pancreas can also coexist with younger cells in an age mosaicism which may give researchers clues as to the aging mechanisms of organs.
Some of our organs may be more resilient when it comes to aging, but all of them will gradually slow down over time, and recent research suggests that we may be able to predict which ones may be the first to go. A study from Stanford University identified at least 87 molecules and microbes present within the body that can be used as biomarkers of aging. Examining how these biomarkers shifted in volunteers for 2 years revealed that people age via different biological mechanisms, finding that they could categorize individuals into different ageotypes by grouping biomarkers based on which organ or system they were most closely associated with.
Evidence of 4 different types of agers were found, based on the dominant aging pathway: kidney, liver, metabolic, and immunity, with some suggesting that others such as cardio agers exist as well. An individual’s agoetype can also be identified which may be down to a combination of genetic and environmental factors, according to Michael Snyder. If this research is correct one day young people may be able to be informed on which aspect of health they need to monitor as they age.
“If you are a cardioager, make sure you watch your bad cholesterol, get your heart checked, exercise,” says Snyder. “For a metabolic ager, watch diet; liver agers, drink less alcohol, etc.”
Although it is not known whether the ageotypes identified will result in physiological changes that may negatively impact health in the long term, Snyder is certain that we are entering an age that is more personalized to approaches that are geared towards anti-aging interventions.
“One-size-fits-all doesn’t cut it,” he says. “Exercise and good diet can help overall, but if your heart or kidney is wearing down you may need to do more directed strategies.”
Deep machine learning advances are also helping scientists to gain more precise estimates of biological aging, one of these approaches involves studying DNA methylation wherein various genes are switched on/off by attaching a methyl chemical group to parts of human DNA. This process is thought to be one of the epigenetic changes to our DNA that determine how our genes are influenced by the environment and our lifestyle. DNA methylation varies with age and our epigenetic patterns change, this allows for the development of epigenetic clocks which are thought to be predictors of biological age.
Epigenetic clocks allow for the comparison of the biological ages of different tissues. Female breast tissue, for example, appears to age faster than the rest of the body. However, even if these clocks prove to be accurate we do not know if treatments to slow down these clocks will also slow down the aging process.
Whatever manner we choose to look at aging through the ultimate goal is to not only slow down aging, but prevent or reverse it if at all possible, and going by science this already appears to be possible at the cellular level. Recent promising research from Stanford University School of Medicine indicates that they were able to rejuvenate cells from elderly donors by making them Yamanaka factor proteins.
However, as promising as this research is, doing something similar to an entire organ may be more challenging. Nevertheless, this work may well be the first step in a process of events that may lead to new treatments that might be able to turn back the biological clock of cells and tissues without having to remove them from the body.
Many scientists are focused on extending the health and lifespan of elderly people through drug discovery. A recent review from the University College London highlights drugs such as rapamycin, metformin and lithium as potential treatments to delay the onset of many of the diseases and problems that accompany old age. However, none of the interventions were able to reverse all of the numerous symptoms of aging. Anti-aging treatments may have tissue specific effects, and some may work synergistically together, the review highlighted the need for a better understanding of how the aging process affects different organs in different ways.
There may be many different ways in which each organ ages, and it makes logical sense to examine them all, and to take care of each of our organs as best as we can to promote healthy aging and longevity. Organs are interconnected systems, and according to Richard Siow, the aging of one organ will inevitably affect the other organs.
“If you have inflammation in your joints, that inflammation is going to impact on your brain and your heart as well,” he says. “Every different organ has a different ageing trajectory, but it’s all interrelated”.
