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One of the major goals of geroscience research is to define ‘biomarkers of aging’ , which can be thought of as individual-level measures of aging that capture inter-individual differences in the timing of disease onset, functional decline, and death over the life course.

There are two kinds of age: chronological age, which is strictly the number of years that something has lived, and biological age refers to how old a person seem. Biological age, also referred to as physiological age, takes many lifestyle factors into consideration, including diet, exercise and sleeping habits, to name a few. Biological age is the superior measure of true age and is an accurate predictor of all-cause mortality.

Biomarkers of aging are biomarkers that could predict functional capacity at some later age better than will chronological age. Stated another way, biomarkers of aging would give the true "biological age", which can be different from the chronological age.

While chronological age is arguably the strongest risk factor for aging-related death and disease, it is important to distinguish chronological time from biological aging. Individuals of the same chronological age may exhibit greatly different susceptibilities to age-related diseases and death, which is likely reflective of differences in their underlying biological aging processes. In the near future, Biomarkers of aging will be crucial to enable evaluation of interventions aimed at promoting healthier aging, by providing a measurable outcome, which unlike incidence of death and/or disease, does not require extremely long follow-up observation.

As of 2019, there are currently there primary biomarkers / clocks.

1. The Epigenetic Clock
The epigenetic clock was developed in 2013. There are currently three epigenetic clock models, namely the clocks of Hannum, Weidner and Horvath.
The epigenetic clock determines the biological age of our cells, tissues and organs. The age estimated by the epigenetic clock is also called the epigenetic age or “DNAm Age”. The epigenetic clock also gives rise to another concept: age acceleration, a measure corresponding to the difference between the age predicted (biological age) by the epigenetic clock and the chronological age.

Like rust on a car, the DNA molecules experience chemical changes that could be interpreted as rust. So, as we age, things change on the molecule, and these changes are methylation, so by measuring the amount of “rust”, you can measure the age.
The epigenetic clock is more accurate than measuring telomere length
The epigenetic clock is the indicator of a biochemical process that plays a role in aging. If you target this process, you slow aging.

Epigenetic changes are considered far more important for aging than telomere maintenance. Telomere shortening alone does not explain aging. Mice have perfect telomeres, but they only live three years.

The epigenetic clock is a biological age estimator and marker of aging. Its robustness and its application to different DNA sources make it the best estimator currently available. The age predicted by DNA methylation allows us to study human development, aging and age-related pathologies. It will become a valuable tool to identify and validate epigenetic anti-aging interventions on humans.

The epigenetic clock is, for many researchers, considered the gold standard of aging biomarkers, as it has a good level of accuracy, although it does have its limitations. For a number of years, Steve Horvath and his team have been working on ways to refine the clock and have now develop a new clock called GrimAge. Referred to as a death clock it can calculate lifespan and the time you have left to live.

2. The Ribosomal Clock RIB
rDNA is considered to be the genomic control key of aging. Epigenetic alterations to DNA methylation has been found to play a key role in the aging process.

Researchers have found that examining just the rDNA of the genome is as accurate as the epigenetic clock, which measures methylation at hundreds of sites on the genome. If this is the case, then this could be a faster and more cost-effective way to measure aging than was previously available.

The clock could be highly useful in combination with therapies that target the aging processes, as any changes in a patient’s biological age would be apparent and confirm that an approach has worked. There are a range of aging biomarkers that researchers currently use; however, they have their limitations, so the recent arrival of the ribosomal clock is most welcome.

3. IMM-AGE Clock
This new, exciting clock analyzes / measures the age of the immune system.

Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual’s immune age.

As we age, our immune systems begin to decline due to many factors, including the thymus shrinking and producing ever-fewer T cells, the ever-increasing chronic inflammation called “inflammaging”, dysfunctional immune cells doing more harm than good, and a lifetime of microbial burden taking its toll. This gradual decline of the immune system is known as immunosenescence.

The efficient function of the immune system is known to be a determinant of longevity, and the immunological model of cancer shows that it plays a central role in your risk of developing cancer. This is no surprise, considering the many functions that the immune system performs and all of the cell types that perform them. From repelling invading pathogens and facilitating wound healing to clearing away cellular garbage, the immune system is the workhorse of the body and essential to life.

In a new study, researchers have shown that it can be a valuable tool for interventions that target the aging processes in order to prevent age-related diseases.

It is currently a challenge to accurately ascertain the state of an individual’s immune system, but this research shows how the IMM-AGE biological clock can be used to analyze the immune system to give an accurate prediction of disease risk and life expectancy.

The IMM-AGE Clock can help track the immune decline that occurs in old age, which is known as immunosenescence. The research team believes that it could provide an “immune age” and be used alongside chronological age to help inform healthcare and drug development.

If the IMM-AGE Clock proves reliable, it could take its place alongside the gold standard for aging biomarkers, the epigenetic clock, along with the newer ribosomal clock. It may prove useful in the development of drugs and vaccines as well as clinical trials in which the aging processes are the focus of therapies. There is certainly a need for more aging biomarkers, so this could potentially be added to the toolkit to help our industry develop therapies.

These promising biomarkers of aging hopefully prove to be beneficial to both basic science and translational research.

Includes Edited Extracts from several Papers including those reviewed by the LEA Foundation
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