Scientists are Modifying Cell Processes to Delay Aging

• Scientists have discovered a potential solution to prevent cells from declining at the pace expected while aging.  

• By intervening in cell aging mechanisms, there’s a chance to rewire the aging control system to encourage a slower decline. 

• This advancement can result in a significantly extended lifespan for humankind.

This article was posted by ScienceDaily: 

After identifying core mechanisms behind the aging process, researchers at the University of California have uncovered two directions cells follow to drive aging. By manipulating this set system, there’s a chance to delay aging for some time. 

These findings, published in Science, explain how innovations in synthetic biology can solve the usual wear and tear cells experience over time. This process is made possible through changes to a core feature of all animal, plant, and human cells—gene regulatory circuits. 

Gene regulatory circuits are part of the backbone of the aging mechanism. This complex structure consists of a network of genes, and the regulatory architecture that controls gene expression. 

Think of gene expression as an instruction manual in your cells, directing how they function. As you age, your expression patterns change, with some genes becoming over or underactive, leading to age-related dysfunctions. 

"These gene circuits can operate like our home electric circuits that control devices like appliances and automobiles," said Professor Nan Hao of the School of Biological Sciences Department of Molecular Biology, the senior author of the study and co-director of UC San Diego's Synthetic Biology Institute. 

But while cells operate on a central gene regulatory circuit, they are not subject to the same aging process or timeline. It is similar to a car deteriorating from engine wear or transmission challenges—while both are valid causes of aging, they don’t have to occur simultaneously to cause degeneration.  

Researchers at the University of California recognized this prospect in cell structure. They developed a "smart aging" process that extends cellular longevity by cycling deterioration from one aging mechanism to another. 

How do Gene Regulatory Circuits Work? 

As mentioned, gene regulatory circuits operate similarly to electric switches found in household appliances, which are usually in two states—on or off. Gene circuits employ positive feedback loops that reinforce the current state, making it stable until an external signal triggers a switch to the alternate form. 

However, rather than a toggle switch, researchers in this study crafted a negative feedback loop to delay aging. This clock-like device makes cells switch back and forth between the two aging states, preventing them from getting stuck in one form for too long.  

To explain, the experts rewired the genes that control cell aging. Instead of these genes working like an on-off switch as seen in household gadgets, they turned them into a sort of biological clock, which they describe as a "gene oscillator."  

By causing this adjustment, cells aren’t left to sit in a potentially detrimental aged condition, leading to cells that live much longer than usual. 

"This is the first time computationally guided synthetic biology, and engineering principles were used to rationally redesign gene circuits and reprogram the aging process to effectively promote longevity," said Hao. These advances are stimulating a potentially new record for life extension in humans. 

However, this isn’t the first time scientists are tinkering with genes to discover new methods for prolonging life. In a 2019 study published in the journal, Evolution Letters, researchers experimented with worms to identify an insulin receptor gene connected with growth and longevity. By working on insulin pathways in these creatures, experts were able to extend the lifespan by more than two times the expected period. 

Scientists have also pieced apart genetic function to properly understand why and how we operate the way we do. Researchers from the University of Cambridge Wellcome Trust-MRC Stem Cell Institute have identified factors that drive cell differentiation using a specialized method to observe stem cells with a single set of chromosomes. 

These experts can pinpoint answers to many biological and medical functioning questions by putting together what makes up cell wiring.  

How Can Gene Regulatory Circuits Delay the Aging Process 

Rewiring gene regulatory circuits is a significant feat for its potential to delay aging. This process can improve aging by influencing DNA repair and cellular stress responses. Genetic rewiring can also target and delay the onset of features like senescence, where cells lose the ability to divide and control. 

Researchers understand the importance of this possibility. In this study, the gene oscillator discovery followed years of research, during which time the team discovered how cells evolve throughout aging. They detected that cells follow a series of molecular changes in life until they degenerate and die. 

However, they identified something else—cells of the same genetic material, located in the same environment, sometimes age through distinct routes. 

On one end, half the cells age through a gradual decline in the stability of their DNA, which houses genetic information. On the other end, aging results from mitochondria deterioration, the energy production unit of cells. 

"Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally designed gene circuits that slow aging," the researchers note in their study. 

​​During research, the team observed Saccharomyces cerevisiae yeast cells as a model of human cells. They found that rewiring yeast cells using the synthetic socially or device considerably increased lifespan by 82%, compared with control cells that were aged under regular settings. This resulted in "the most pronounced lifespan extension in yeast that we have observed with genetic perturbations." 

Hao described this impressive feat, saying: "Our oscillator cells live longer than any of the longest-lived strains previously identified by unbiased genetic screens".  

Scientific innovations are redesigning new possibilities for how we live life, and how long we get to do so. The researchers put it best: “Our work represents a proof-of-concept example, demonstrating the successful application of synthetic biology to reprogram the cellular aging process.” They add that this research: “may lay the foundation for designing synthetic gene circuits to effectively promote longevity in more complex organisms." 

References:

Harris SE, Riggio V, Evenden L, et al. Age-related gene expression changes, and transcriptome wide association study of physical and cognitive aging traits, in the Lothian Birth Cohort 1936. Aging (Albany NY). 2017;9(12):2489-2503. doi:10.18632/aging.101333 

Lind, M. A., et al. 2019. Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring. Evolution Letters 

Leeb M, Dietmann S, Paramor M, Niwa H, Smith A. Genetic exploration of the exit from self-renewal using haploid embryonic stem cells. Cell Stem Cell. 2014;14(3):385-393. doi:10.1016/j.stem.2013.12.008