The Golgi Apparatus is More Than Just a Post Office for the Cell: It can Mitigate Ageing Responses.
Researchers Hee-sung Choi (left) and Katie Dehesh (right) holding young and aged Thale Cress (Arabidopsis thaliana) respectively (2).
When it comes to human aging research, it is easy to imagine a lab full of stem cell samples of animals like rodents and flat worms used to crack the mystery of aging. Restoring a mice’s eyesight and rejuvenating tissues using stem cells already are being accomplished, and the current 191.5 billon dollar global anti-aging market is predicted to explode into a 421.4 billion industry by 2030 (6).
The scope of research has been mostly limited to animals. In hindsight, this appears logical: the aim is to solve human aging, so it only makes sense to research species closest to humans. However, a recent study by Hee-sung Choi and other University of Santa Barbara Department of Botany and Plant Sciences researchers in October 2023, uncovered a novel method of researching human aging with green plants (2). The group discovered that the Golgi apparatus, a cellular machinery commonly known to process the transport of secretory proteins, could be a key to controlling aging. They proposed that investigating plants can be a novel way to study the role of Golgi in aging.
The Research
Choi’s group found that altering a key protein of the Golgi apparatus could confer a direct effect on the cell’s aging processes. (2) They used Thale Cress, a small plant part of the mustard family, examining the effect of creating a mutation in the conserved oligomeric Golgi complex (COG), which is a protein compound responsible for organizing the flow of secretory proteins) on the stress response of the plant (1). Composed of eight proteins, the COG complex is further divided into two subunits Lobe A and Lobe B. The Choi’s group modified the conserved oligomeric Golgi protein 7 (COG7), to build a dysfunctional COG7 (1). The Researchers then compared the regular wild-type strain and the dysfunctional COG7 mutant strain (cog7 mutant) under various stress-inducing conditions (1). Although the two variant proteins, COG7 and cog7 mutant, performed exactly the same under ideal conditions with sufficient lighting and nutrition, the researchers observed a significantly accelerated aging response in cog 7 mutants under light stress with nutritional deficiency (1).
The aging response they observed is senescence, a coordinated degradation of old tissues for the reallocation of the recycled resources to juvenile or reproductive parts of the plant (3). For example, the bottom leaves of a plant wilting yellow is a senescence response that translocates the resources to newly developing foliages. Senescence happens to various cues such as simple age, disease, poor lighting, and lack of nutrients. The case UCR researchers found is the senescence wrought by lack of sucrose, a necessary sugar required for the plant’s growth, and light, a factor crucial for photosynthesis.
So what happened to the cog7 mutants exactly? It turns out that the mutation induced a more sensitive response towards lack of light, expressing a critical senescence response as early as three days after darkness when the unaffected strain took nine days to reach the same level of senescence (2).
The numbers at the top indicate days after dark treatment for wild-type (WT) and the cog7 mutant (1).
From the diagram above, it is apparent the leaves of cog7 more rapidly develop yellow leaves in darkness. The yellowness is the result of rapid degradation of large amounts of chlorophyll, which is referred to as Chlorosis. It is typical a senescence response exhibited by plants trying to transport out the chlorophyll in aged leaves before dropping the leaves down. What’s more, Choi’s group noticed that the macroscopic difference in the leaf color suggesting accelerated senescence was also backed by the change on the molecular scales.
One major microscopic difference the researchers discovered is the difference between the wildtype and the cog 7 mutant’s concentration of compounds responsible for decomposing large molecules (1). One of those compounds is Ubiquitin proteome system (UPS), a cellular mechanism that creates proteasomes–small machines that are able to break down proteins (4). The abundance of UPS indicates the progression of senescence because recycling the proteins for a programmed senescence induced leaf death requires the decomposition and transport of the proteins in the aged leaf tissues (4). Because the molecule ubiquitin is required for synthesizing UPS, its concentration correlates to the abundance of UPS in the cell. The researchers assayed for the abundance of ubiquitin using immunoblot (a technique used to detect protein with antibodies of the target protein), the results indicated that the cog 7 mutant plants reached levels of ubiquitin typical of a six day old wildtype in just three days, indicating the mutant plants reached higher concentrations of ubiquitin faster, and therefore a higher UPS concentration for accelerated senescence.
Immunoblot assay results of the wild-type (WT) and the cog7 mutant. The cog7/COG7 group was a positive control of the experiment. Darker colors indicate larger quantities of ubiquitin in the sample. The numbers at the top indicate days after dark treatment (1).
Nevertheless, the darkness did not mean an irreversible end for the cog7 mutants. When the researchers overexpressed another protein in the same COG complex subunit COG5, the results indicated a visible reversal of the senescence displayed by the mutants (1). Based on this, the researchers hypothesize that COG7 and COG5 likely have overlapping functions in their subunit, which allows COG5 to compensate for the loss of COG7’s function (1). This means that even when senescence occurs due to a malfunction of the Golgi, it could be remedied by supplying the cell with more COG proteins (2).
Why Does This Matter?
All this discovery of a dysfunctional COG7’s effect on accelerated senescence pioneers new opportunities to research human aging using plants (2). Of course, the findings could be used to slow down plant aging as maintaining a strong plant directly correlates to the harvest yield, resistance to disease, and the span of the growing season; however, Choi’s research can be extended to humans thanks to the conserved nature of the COG complex. Being conserved in Biology means it is present across a wide variety of species. COG7, or even the entire COG complex of the Golgi body is conserved among all eukaryotes, meaning the exact protein can be found in plants, yeast, worms, and humans. Also, senescence, though the physiological effects and purpose differ between plants and animals, is also a conserved process among multicellular eukaryotes. For animals, senescence is not a programmed manoeuvre to redirect resources for juvenile parts. Instead, senescence is directly associated with the effects of aging commonly thought of–loss of motility and health (5). It is also reported to play a crucial role in dispersing the damaging effects of stress for animals (4). Therefore, the UCR researcher believes studying the COG complex through plants could lay the groundwork for a new domain of aging research for humans. In fact, the next goal of Choi’s group is to analyze the molecular dynamics of cog7’s function to better understand exactly how aging is induced by the dysfunctional COG7 protein (2).
It is true that there is much work ahead to fully understand how the Golgi body, previously thought of only governing protein trafficking, could also influence the aging effects of an organism. However, the discovery brings a refreshing wind to the scientific community, where researchers can exploit the Golgi to delay aging in plants and humans.
References
1. Choi, Hee-Seung, et al. "COG-imposed Golgi functional integrity determines the onset of dark-induced senescence." Nature Plants 9.11 (2023): 1890-1901, https://www.nature.com/articles/s41477-023-01545-3#citeas.
2. Bernstein, Jules. “Keys to Aging Hidden in the Leaves.” UC Riverside News, 17 January 2024, https://news.ucr.edu/articles/2024/01/17/keys-aging-hidden-leaves.
3. Mayta, M. L., et al. "Leaf senescence: the chloroplast connection comes of age. Plants 8 (11): 495." (2019), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918220/.
4. Wang, H., and J. H. Schippers. "The role and regulation of autophagy and the proteasome during aging and senescence in plants. Genes 10 (4): 267." (2019), https://www.mdpi.com/2073-4425/10/4/267.
5. Britannica Writer. “Senescence in Mammals.” Britannica, https://www.britannica.com/science/aging-life-process/Senescence-in-mammals.
6. Jimenez, Darcy .“Billionaires are Betting on Anti-ageing Research, but can Ageing Really be Cured?” Pharmaceutical Technology, 16 September 2021, https://www.pharmaceutical-technology.com/features/billionaires-anti-ageing-research/.
