Chronological age and biological age
Defining aging solely on the basis of chronological age the trivial counting revolutions of the Earth around the Sun since we were born, is reductive. Two people born in the same year can have two very different states of health and two very different aging processes. Thus was born the search for new definitions of age that would account for health status and be able to predict the propensity of getting sick or staying healthy, and especially that would be based on indicators of physiological body function and molecular biomarkers.
Among the pioneers in the development of these “biological clocks” is Steve Horvath, a biogerontologist and biostatistician, who in 2013 published a study of his epigenetic biological clock based on DNA methylation (link to the study here).
The rules for defining a biological clock
Horvath defined four conditions that determine whether a biological clock is sensible and functional: it must be able to provide a quantitative measure that correlates with age; it must be applicable to all mammals; it must apply to most types of cells (and thus it must apply to different organs and tissues); it must be able to predict mortality, risk of getting sick, and general decline in health status; and finally, it must be applicable even to cells studied in the laboratory.
Considering the complexity of the human organism, however, defining a global biological ageDifferent from chronological age. It is a measure of the body's ageing, based on the effectiveness of the mechanisms that keep cells young and on markers of the functionality of organs and apparatus. is no easy task; therefore, most studies initially focused on defining the biological age of individual tissues and organs.
Horvath defined four conditions that determine whether a biological clock is meaningful and functional: it must be able to provide a quantitative measure that correlates with age; it must be applicable to all mammals; it must apply to most cell types; and it must be able to predict health status.
The role of methylation
The epigenetic clock developed by Horvath considers the change in methylation processes of certain genes as the primary indicator of biological age. Let’s see what this is all about. The identity of cells, their specialization and even their ability to function properly are established by two components: genetics, which is the set of biological information that a cell has at its disposal, andepigeneticsLiterally "above genetics." This term refers to all biochemical processes which, without modifying the DNA sequence, affect the expression of genes, both "switching them on" and "switching them off"., which is the modifications of the DNA that do not change the genetic code, but change its structure and influence the way genes are read and expressed in a cell.
Example of the epigenetic mechanisms involved in the “packing” of DNA
Among the key epigenetic processes in the development, differentiation and maintenance of “cellular identity” is methylation. Put simply, it is a mechanism that regulates the genetic expression of cells through the transport of methyl groups that associate with nitrogenous bases in the DNA. Along with other epigenetic processes, methylation plays a central role in processes leading to disease development and also in aging processes, and many studies have identified it as a good marker of age for various tissues.
The epigenetic clock developed by Horvath considers the change in the methylation processes of certain genes as the primary indicator of biological age.
Horvath’s Clock
Aiming to find an age predictor to estimate the DNA methylation age of most tissues and cell types, Horvath considered 8,000 samples from theIllumina DNA methylation array -a database that contains DNA methylation levels at various locations in the human genome. The data covered 51 tissues and several healthy cell types. Systematic analysis of the samples made it possible to draw up a number of properties regarding the “age of DNA methylation”.For example, that it is close to zero for embryonic stem cells, that it correlates with the number of cell passages, that the “epigenetic aging rate” is heritable , and that it is also applicable to chimpanzee tissues.
In a follow-up study conducted in Italy ((link here)on families consisting of supercentenarians and their offspring aged 71 years on average, Horvath and the group of Italian researchers observed that, epigenetically, centenarians are 8.6 years younger on average than their chronological age, and that the offspring have a lower epigenetic age than control subjects of the same age, by about 5.1 years..
Horvath’s idea, then, is that the age of DNA methylation is a cumulative measure of the degree of epigenetic maintenance in an organism: whereas the aging process in each tissue or organ is related to specific cellular mutations, methylation is a process that correlates closely with age and affects all tissues in an organism.
The epigenetic clock proposed in 2013, therefore, can be used as a parameter to answer a number of questions in the biology of development, cancer and aging. In one of the most recent studies, published last year (link here), Horvath was also able to estimate a methylation-based biological age valid for 59 tissue types in 128 mammalian species.
