Healthy Aging is a Harmful Concept that will Misdirect Research Efforts


Pioneer Founding member

"Healthy aging" is a popular concept in the research community. It is the idea that aging is somehow separate from age-related disease, and if we could just effectively treat age-related disease, then people would have a healthier old age, but the shape and length of life would be much the same. This is very wrong-headed. Aging (whatever parts of the decline one is willing to say are not age-related disease) and age-related diseases (the large declines in function that everyone acknowledges are bad) arise from the same underlying mechanisms, the accumulation of cell and tissue damage and the consequences of that damage. The only difference is a matter of degree.

Trying to cure age-related disease without repairing the underlying damage that causes aging is futile. We know it is futile because this is exactly the strategy that the scientific and medical community have been following, at enormous expense and investment of time, in past decades. There is only marginal, incremental progress to show for this effort. Yet as soon as just one method of repairing damage, the clearance of senescent cells, started development in earnest, less than a decade ago, it resulted in easily obtained benefits in animal studies. Now the effects of senolytic drugs to selectively kill senescent cells threaten to be much larger and more reliable in the treatment of age-related disease and dysfunction than anything achieved to date by the rest of the field of medicine.

This open access paper, in which the authors give a summary of the present lack of good biomarkers for aging, is an example of the way in which the concept of healthy aging steers research strategy in the wrong direction. Researchers invested in this concept will try to square the circle, in search of ways to distinguish age-related disease from aging. They will draw lines and declare some of aging, and the suffering and declining function it causes, to be completely acceptable and thus not worthy of treatment. This is all madness, and the concept of healthy aging should be consigned to the pit, never to be seen again.

Hallmarks of senescence and aging

Every living organism lives in a permanent struggle with extrinsic and intrinsic agents that can damage it. Without its own repair mechanisms, life of living creatures would be extremely short, since the accumulation of harmful substances would damage the cellular elements, their function, which would ultimately result in damage to the various tissues and accelerated aging of the entire organism. Most of the aging definition involves a gradual, heterogeneous impair in the structure, function, and maintenance of repair systems of various organs and an increased inclination to various diseases. One could say that the age/aging phases are easy to recognize, but the mechanisms responsible for the aging process are difficult to define and harder to prove. Technological progress has established various methodological approaches to detect some cellular and molecular mechanisms associated with aging. Among others, scientists have focused recently on senescence (cellular aging, biological aging) mechanisms as one of the key factor in a complex aging process.

Aging is an intrinsic feature of all living beings. The complex process of biological aging is the result of genetic and, to a greater extent, environmental factors and time. It occurs heterogeneously across multiple cells and tissues. As the rate of aging is not the same in all humans, the biological age does not have to be in accordance with the chronological age. Many age-associated changes and hallmarks are evident in the human body. In the background of all the changes that occur during aging are three key factors - inflammation, immune aging, and senescence.

In order to examine why and how people become old with different rate, it is necessary to define the primary indicators/biomarkers of the healthy aging process. Only in this way it will be possible to distinguish the phenomenon of aging due to the processes caused by various diseases that are commonly associated with the aging process. In this sense, the scientific community is continually investing great efforts in discovering such biomarkers.

According to the American Federation for Aging Research recommendations, aging biomarkers should meet several criteria. They have to: 1. predict the rate of aging (correlate with aging); 2. monitor a basic process that underlies the aging process (determine "healthy aging", not the effects of disease); 3. be able to be tested repeatedly without harming the person; 4. be applicable to humans and animals. However, currently, there is no biomarker that would meet all of these criteria. Currently, due to the stated fact that many of the hallmarks of aging do not meet biomarker definition criteria, it may be better to use terms a) hallmarks of senescent cells or hallmarks of aging or b) possible biomarkers of senescence.

Thus in summary, there are currently no standardized biomarkers of cellular aging process or the healthy aging of the organism. Biomarkers described in literature do not meet all criteria of an ideal aging biomarker and actually represent various hallmarks of the aging process. Most biomarkers currently being examined as senescence or aging biomarkers are related to age-related illnesses rather than the process of healthy aging. As the effector mechanisms of senescence are neither necessarily specific to senescence nor present in all forms of senescence (the rate of senescence is not the same for all types of cells), the interpretation of existing biomarkers of senescence (for now the hallmarks or possible biomarkers) should be context dependent. Additionally, a combination of multiple biomarkers should be used.

Detection of biomarkers, in particular their quantification and validation, are necessary for understanding the senescence processes (diagnostic biomarkers), monitoring of the rate of senescence (prognostic and predictive biomarkers) and the possible use of appropriate therapy intervention (pharmacodynamic biomarkers). The discovery and selection of reliable biomarkers, and the use of reproducible methods could help to better understanding of complex web of senescence and aging processes, but it will also open some new questions. Despite new findings at the cellular and molecular level the understanding the aging process is still limited.