Today's research materials are representative of numerous initiatives aiming to produce taxonomies of the biochemistry of aging, to catalog the observed variations. Yet, with the exception of a very small number of unlucky souls bearing rare harmful mutations, we all age for the same underlying reasons. The same processes of metabolism produce the same forms of cell and tissue damage, leading to the same downstream dysfunctions and the same ultimately fatal age-related conditions. Yes, there is some variation in outcome. For all that aging is a universally similar process of multiple interacting forms of damage, some portions of its consequences progress modestly more rapidly or modestly more slowly from individual to individual, a distribution of outcomes that largely results from lifestyle choices and random happenstance, rather than from genetic variation.
Thus many researchers are interested in this distribution, perhaps more so than in doing something about the challenge of aging, the death and suffering it causes. Given this view of the situation, I would say that somewhat more scientific effort goes into cataloging the differences between individuals than is merited. Examining long-lived people, with the goal of producing interventions that might make more people live incrementally longer in good health, is a terrible strategy, when compared with the alternative of directly addressing the common causes of aging, which might make everyone live considerably longer in good health. Nonetheless, despite the great potential of rejuvenation biotechnology based on repair of the damage that causes aging, there is a lot more funding and interest in the research community for far less promising lines of work.
Researchers profiled a group of 43 healthy men and women between the ages of 34 and 68, taking extensive measurements of their molecular biology at least five times over two years. The researchers determined that people generally age along certain biological pathways in the body: metabolic, immune, hepatic (liver) and nephrotic (kidney). People who are metabolic agers, for example, might be at a higher risk for diabetes or show signs of elevated hemoglobin A1c, a measure of blood-sugar levels, as they grow older. People with an immune ageotype, on the other hand, might generate higher levels of inflammatory markers or be more prone to immune-related diseases as they age. But the ageotypes are not mutually exclusive, and a metabolic ager could also be an immune ager, for example.
Just because an individual falls into one or more of the four ageotypes - metabolic, immune, hepatic and nephrotic - doesn't mean that they're not also aging along the other biological pathways. The ageotype signifies the pathways in which increases in aging biomarkers are most pronounced. Perhaps most exciting - and surprising - is that not everyone in the study showed an increase in ageotype markers over time. In some people, their markers decreased, at least for a short period, when they changed their behavior. They still aged, but the overall rate at which they did so declined, and in some cases aging markers decreased. In fact, the team saw this phenomenon occur in a handful of important clinical molecules, including hemoglobin A1c and creatine, a marker for kidney function, among a small subset of participants.
In that subset, there were individuals who made lifestyle changes to slow their aging rate. Among those who exhibited decreased levels of hemoglobin A1c, many had lost weight, and one made dietary changes. Some who saw a decrease in creatine, indicating improved kidney function, were taking statins. In other cases, exactly why rates of aging markers waned was unclear. For some people, there were no obvious behavioral changes, yet the team still saw a decreased rate of aging along their ageotype pathways. There was also a handful of people that maintained a slower-than-average aging rate throughout the entire study. How or why is still a mystery.
The molecular changes that occur with aging are not well understood. Here, we performed longitudinal and deep multiomics profiling of 106 healthy individuals from 29 to 75 years of age and examined how different types of 'omic' measurements, including transcripts, proteins, metabolites, cytokines, microbes, and clinical laboratory values, correlate with age. We identified both known and new markers that associated with age, as well as distinct molecular patterns of aging in insulin-resistant as compared to insulin-sensitive individuals. In a longitudinal setting, we identified personal aging markers whose levels changed over a short time frame of 2-3 years. Further, we defined different types of aging patterns in different individuals, termed 'ageotypes', on the basis of the types of molecular pathways that changed over time in a given individual. Ageotypes may provide a molecular assessment of personal aging, reflective of personal lifestyle and medical history, that may ultimately be useful in monitoring and intervening in the aging process.