Before we get to the epigenetic clock. It worth clarifying what epigenetics is. It deals with the inheritance of genes that occur without altering the DNA sequence. The impact of epigenetic processes on the body is most evident in cell development. Defective DNA methylation can be linked to diseases such as dementia or hearing loss.
The epigenetic clock is a biochemical test that can calculate age. It is based on DNA methylation levels, counting the accumulation of methyl groups in DNA molecules. DNA methylation is a biological process whereby methyl groups are added to the DNA molecule. It changes the activity of a DNA strand without changing the sequence. The strong effects of age on DNA methylation levels have been known since the 1960s. The first evidence that DNA methylation levels in saliva can generate age power signals with an average accuracy of 5.2 years was published by a UCLA team in 2011.
Steve Horvath, a German American ageing researcher and geneticist, has identified 353 predictive regions, called CpG islands, in human DNA where cytosine nucleotides are followed by guanine nucleotides, which can be used to determine a person’s chronological age. It is not yet known exactly what the DNA methylation age measures. It is supposed to measure the cumulative effect of an epigenetic maintenance system, but the details are not known. However, the fact that the DNA methylation age of blood predicts all causes of death in later life has been inferred to be linked to a process that causes ageing. However, if CpG were to play a direct casual role in the ageing process, then mortality caused by it would be less likely to be observed in older individuals, and so would be unlikely to have been chosen as a predictor. So, therefore, it is also likely that 353 clocks of CpG have no casual effect. Rather, it captures the epigenome and its emergent property.
In 2010, a new unifying model of ageing and complex disease development was proposed, incorporating classical ageing theories and epigenetics. Horvath and Raj developed the theory and proposed the epigenetic clock theory with the following principles. Biological aging as a developmental and maintenance program is an unintended consequence with molecular traces of DNA methylation as age estimates. The precise mechanism linking innate molecular processes to issue decline. They are associated with both intracellular changes and subtle changes in cellular composition, such as fully functional somatic stem cells. Alternatively, at the molecular level, the aging of DNA methylation is a proximal readout of a collection of innate aging processes that, in concert with other, unrelated root causes of aging, cause impairment of tissue function.
Biological ageing clocks and biomarkers are expected to find many applications in biological research. Due the fact that age is the main characteristic of the organism. The following are some of the areas where accurate measurement of age may be useful. Testing the validity of different theories of biological ageing, diagnosing various age-related diseases, and identifying subtypes of cancer. It can also be use in predicting the onset of other diseases, as surrogate markers for evaluation of therapeutic inventions, including rejuvenation approaches to study developmental biology and cell differentiation. Or, even forensic application, such as estimating the age of a suspect based on a blood sample left at the scene.
The biological mechanism behind the epigenetic clock is now unknown. However, they can help answer long-standing questions in several areas. Including the important question of why do we age? To this end, it would be useful to make a comparison and find a link between the epigenetic clock and the transcriptome’s readout of the ageing clock. The following explanations are currently available in the literature. Horvath assumes that the clock originates from a footprint left by an epigenomic maintenance system. Another possible is unpaired DNA damage.
These are common including about fifty double stranded DNA breaks per cell cycle and oxidative damage, which occurs about 10.000 times a day. Many epigenetic changes occur during repair of double-strand breaks, and some of these epigenetic changes persist after repair, including increased methylation of CpG island promoters. Similar but transient epigenetic changes have recently been found in oxidative damage caused by hydrogen peroxide (H2O2) and it has been suggested that epigenetic changes may persist after repair. Therefore, these changes may contribute to the epigenetic clock. These epigenetic alterations may parallel the accumulation of unpaired DNA damage and have been proposed to cause ageing.
In conclusion, biological clocks are expected to be useful in studying the causes of aging and the defense against it. However, only influencing the rate of future aging, i.e., the slope of the Gompertz curve, the time at which mortality increases to age, but not interventions that have an effect, for example, reduce the intersection of the Gompertz curve at every age of the mortal. The Gompertz-Makeham law is nothing more than the sum of the human death rate with an age-dependent component that increases exponentially with age and an age independent component.
Information collected by Dezső Sándor.