Researchers from Oregon State University have discovered a subset of circadian genes that only become active as an organism ages or during times of stress. They could provide a new lens through which to view the process of cellular aging.
Virtually every animal on earth has a circadian rhythm – a roughly 24-hour biological, internal clock. This daily ebb and flow is driven by similar genetic mechanisms throughout the animal kingdom.
Even down to the humble fruit fly, the genetic fingerprint of circadian rhythmicity is the same.
Our body’s natural clock oversees a wide array of biological pathways.
The study of these intriguing rhythms and their implications has advanced in leaps and bounds over recent decades, but there is still much to learn, especially regarding their role in disease.
One only needs to recall the psychological and physiological effects of jet lag to understand how significant circadian rhythms are to well-being.
Although the sleep/wake cycle affected by jet lag is the most obvious role of circadian rhythms, it is only a small cog in a huge and complex machine. The genes involved oversee a myriad of biochemical processes.
Disrupted circadian rhythms have been linked to a number of illnesses; from psychiatric and neurodegenerative diseases to cancer. There is also evidence that interference with the biological clock might shorten overall lifespan.
Although disturbed circadian cycles have been implicated in these detrimental processes, exactly how the biological clock protects an organism from age- and stress-related degeneration has not been understood. A study, published this week in Nature Communications, shines a light on a potential key player.
As we age, some of our body clock’s genes maintain their rhythmicity, while others steadily drift out of sync. A research team, led by Rachael Kuintzle, recently uncovered a set of genes that buck this trend, referred to as late-life cyclers (LLCs).
In their study on Drosophila fruit flies, these genes were shown only to become active later in life, or during bouts of intense stress.
“This class of LLC genes appear to become active and respond to some of the stresses most common in aging, such as cellular and molecular damage, oxidative stress, or even some disease states.”
Co-senior author Jadwiga Giebultowicz, professor in the OSU College of Science
As individuals age, there tends to be neural degeneration, reduction in memory, and other cognitive issues; these problems become worse if the biological clock is experimentally disrupted. The authors believe that LLC genes are a response to this and are called into action to help protect the nervous system.
As aging marches on, LLC genes become more and more active. They appear to play a role in sequestering improperly folded proteins or helping them to fold correctly again. In certain neurodegenerative diseases, such as Alzheimer’s disease, protein aggregation is known to play a part; LLC genes might help prevent their buildup.
According to David Hendrix, co-senior author of the study:
“Discovery of LLC genes may provide a missing link, the answer to why the disruption of circadian clocks accelerates aging symptoms.”
The researchers found that when they created oxidative stress in young fruit flies, LLC genes became rhythmically active. “In experiments where we created artificial oxidative stress in young fruit flies, the LLC genes were rhythmically activated,” according to Eileen Chow, an Oregon State University faculty research assistant and co-author of the study.
“Some of these same genes are known to be more active in people who have cancer. They appear to be a double-edged sword, necessary during times of stress but possibly harmful if activated all the time,” she adds.
Genes controlling circadian rhythms, including LLC genes, are found throughout the nervous system and peripheral organs. They have an influence on a range of processes and behaviors from the obvious, like sleep, through to feeding patterns, fertility, DNA repair, and the effectiveness of medications.
Because circadian rhythms are so integral and influential to health and disease, new discoveries could have large-scale implications for developing the medical interventions of the future. By better understanding this new group of genes, it might eventually be possible to manipulate them into action or dampen their response.