The epigenetics of aging and the biological clock

Alan Horsager, Ph.D.
June 11, 2018

Time marches on. We all age. At least, chronologically.

What if there were ways to control our aging, at least biologically? Or even reverse it? Many people who conduct aging research agree that biological aging is not a given and, at least in principle, a person's biological clock can be reversed.

What exactly does it mean to age? There are several theories on aging but one category of theories, called error theory, suggests that micro-insults aggregate within cells and DNA that leads to aging. In error theory, aging involves an accumulation of modifications to the DNA that degrades the function of your body's cells. 

It's thought that this clock is reset at the point of conception and essentially all these modifications are "wiped away" and the embryo begins with a clean slate. However, it's worth looking at the growing studies around transgenerational epigenetic inheritance that suggest some of these modifications are inherited across generations.

Several scientific groups, including Dr. Izpisua Belmonte's group at the Salk Institute, see the epigenome as the mechanism for the biological clock. The epigenome is a system of molecules that wrap around the DNA and control which genes are active and which are suppressed. It provides the biological plan for the body to work properly. However, several factors have been shown to corrupt this plan, which may be part of the reason we age. 

After fertilization and the embryo begins to develop into a little person, the epigenome plays an essential role by telling cells which type they should become - neuron, skin, bone, etc. The epigenome thus provides the script for proper cell differentiation and function to make up your body. 

The epigenome continues to provide the proper script for new cells so they know their function after they're formed. The epigenetic pattern can also change based on specific signals from the environment so that cells can continue to function properly under different conditions. Everything from exercise to smoking can cause the epigenome to change.

It's thought that not only does the state of the epigenome serve as a good biomarker for predicting biological age, it very well may be a cause. If the epigenome is altered, perhaps the cells and body become less able to do their job.

Looking at how epigenetic age may vary within a group of people with the same chronological age could help us understand how various environmental factors contribute to the slowing or acceleration of human aging. What is particularly exciting (and hopeful!) is that the epigenome is a dynamic, flexible system that can be changed or reversed, suggesting that the epigenome may serve as a good marker for the success of various anti-aging interventions.

There is a rich body of scientific literature that shows the epigenome, specifically DNA methylation, changes with chronological age. Not surprisingly, several groups have developed epigenetic clocks for predicting biological age. An "epigenetic clock" is set of methylation sites across the genome that are analyzed using computational methods to estimate the age of the tested DNA. Each individual methylation site isn't very predictive of age but, in aggregate, the whole methylation or epigenetic profile is very predictive. In this case, the whole is greater than the sum of its parts.

As mentioned above, it isn't interesting when it predicts chronological age. It's when deviations from chronological age occur that things start to get interesting.

When scientific researchers try to predict epigenetic age, they generally find outliers. These are people that have epigenetic ages that don't directly line up with their chronological age. Some of these folks have epigenetic ages that are greater than their chronological age (biologically older) and some have an epigenetic age that is less than their chronological age (biologically younger).

The importance of determining if someone is biologically older by looking at their epigenetic profile can be appreciated when you realize those profiles are associated with a number of age-related conditions and diseases. Increased biological age (through an epigenetic analysis) is associated with neuropathology in the elderly, Down syndrome, Parkinson's disease, Werner syndrome, and physical/cognitive fitness. In addition to being predictive of all-cause mortality, these aging clocks are predictive of the development of certain types of cancers. A meta-analysis of DNA methylation in over 13,000, racially-diverse subjects was found to predict life expectancy due to all-cause mortality, cause-specific death, coronary heart disease, and health status. The epigenetic profile also predicts certain lifestyle and demographic factors, including education, income, exercise, blood pressure, body mass index (BMI), fruit and vegetable intake, and smoking.

These large-scale epidemiological studies have established that epigenetic age is associated with congenital and age-related conditions, lifestyle, and environment. Certainly more studies are needed and we will likely see others that point out associations with other health conditions and diseases.

But taken together, these data support the idea that epigenetic biomarkers could be used for anti-aging interventions that include measuring the impact of improved health factors such as healthy diet, physical exercise, and avoiding obesity. 

© 2018 | Relative Health, Inc.