Aging Gracefully Linked to RNA Splicing

Highlights

• Researchers studied RNA splicing to understand its influence on aging.
• RNA splicing found to be a biomarker for aging.
• Premature aging could be detected using RNA splicing. Splicing Factor 1 found to play a key role in RNA splicing

Aging is a strong risk factor for diseases, however, the mechanism that promotes aging is not well understood. Researchers from The Harvard Chan Institute of Public Health have found that the longevity of roundworms was associated with RNA splicing. This study raises hope that altering splicing factors would aid in healthy aging. Senior author of the study, Dr. William Mair, an assistant professor of genetics and complex diseases at Harvard Chan School said, “What kills neurons in Alzheimer's is certainly different from what causes cardiovascular disease, but the shared underlying risk factor for these illnesses is really age itself. So one of the big questions is: Is there a unifying theme that unfolds molecularly within various organ systems and allows these diseases to take hold?"

Increase in Life Expectancy

People are living for more number of years as advancements in medical technology have served to increase life expectancy.

However, increase in the number of years has not necessarily translated to quality of life. Many old people suffer from some form of cancer or neurodegenerative disease or even heart disease.

Bodies will function ‘youthfully’ when the central dogma, DNA to RNA to protein synthesis is maintained without any disruptions. There is very little that is known about the influence of RNA splicing on aging.

Dr. Mair continues, "Although we know that specific splicing defects can lead to disease, we were really intrigued about de-regulation of RNA splicing as a driver of the aging process itself, because practically nothing is known about that. Put simply, splicing is a way for organisms to generate complexity from a relatively limited number of genes."

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Caenorhabditis elegans

The researchers studied RNA splicing and aging on the roundworm Caenorhabditis elegans. The round worm was chosen for experimental studies because

• Roundworms live only for three weeks, therefore it gives the researchers an ability to study aging over a short period of time.
• It shows distinctive signs of aging.
• Their skin wrinkles over age and there is a reduction in fertility as well as immune response.
• The skin of Caenorhabditis elegans is transparent so the researchers could use fluorescent genetic tools to visualize splicing.

The researchers found that the RNA splicing was distinct when it was youthful and could easily detect premature aging. This lead the researchers to believe that RNA splicing could be an effective tool in the detection of aging.

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When the researchers enforced dietary restrictions, youthful splicing was noticed throughout the lifespan, stressing the importance of diet in RNA splicing and, subsequently, on old age.

Splicing factor 1 (SFA-1)

The splicing factor 1 is found in both humans as well as in roundworms and is associated with many aging experiments. If this factor is present in abundance, then it will independently increase lifespan.

RNA splicing in Aging

Previous studies have shown that RNA splicing could play a key role in neurodegenerative disorders.RNA splicing  that is noticed in cognitively healthy aged individuals has been found in 95% of individuals with frontotemporal lobar degeneration and in Alzheimer’s, irrespective of the age.

RNA splicing has never been fully detailed with aging in mind. DNA as well as protein formed have all been studied with respect to aging, however, such studies show that there are other mechanisms which could play a key role in aging. This study has shown that RNA splicing might not only increase lifespan but it could also lead to healthier aging.

 

References:

1. Analysis of alternative splicing associated with aging and neurodegeneration in the human brain - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202275/)

Source-Medindia