The nematode, Caenorhabditis elegans, used for the genetic analysis.
From a superstitious creationists point of view there are two ways to interpret the findings of a team of researchers from the Buck Institute, Sanford Burnham Prebys and Rutgers University, who have uncovered possible novel functions for various autophagy genes, which may control different forms of disposal including misfolded proteins—and ultimately affect aging. Unfortunately either choice creates unresolvable paradoxes, unlike the Theory of Evolution which fully explains the facts without resorting to the childish ideas of magic and omniscient, omnipotent designers:
- Either the 'designer' designed these genes to clean up the mistakes its earlier designs produced, but they eventually stop doing so (so we die).
- Or it designed them to ensure we died of old age, by not cleaning up the mess its earlier design makes.
They also claim 'death' didn't 'enter the world' (as though 'death' is some sort of physical entity) until 'The Fall' when a mythical couple did something they were designed to do and exercised free will. Somehow this created 'death' (as well as lots of parasitic pathogens, allegedly). But these genes are part of the 'design' so were species like humans created with these genes (in which case the 'designer' was planning for 'The Fall' and 'The Fall' was all part of its plan), or did it redesign us afterwards to incorporate the new 'death' thing to ensure we die of old age, if one of its pathogens doesn't get us first.
The same case can be made for the immune system - were we originally 'designed' with it to protect us from the pathogens that didn't yet exist, in which case the 'designer' was planning to harm us with pathogens, or was there an upgrade, post-Fall, that the designer 'forgot' to mention in its account of how it magicked humans out of dirt?
Sadly for creationism, these are the sorts of irreconcilable paradoxes that their childish superstition contains, which is why they need to perform so much in the way of mental gymnastics to continue to pretend they have a coherent and logical set of beliefs.
So, what are these findings which yet again refute the childish notion of creationism? A news release from the Buck Institute explains:
Autophagy, which declines with age, may hold more mysteries than researchers previously suspected. In the January 4th issue of Nature Aging, it was noted that scientists from the Buck Institute, Sanford Burnham Prebys and Rutgers University have uncovered possible novel functions for various autophagy genes, which may control different forms of disposal including misfolded proteins—and ultimately affect aging.In the abstract to their paper in the journal Nature Aging, which sadly is behind a paywall, the authors say:
“While this is very basic research, this work is a reminder that it is critical for us to understand whether we have the whole story about the different genes that have been related to aging or age-related diseases,” said Professor Malene Hansen, Ph.D., Buck’s chief scientific officer, who is also the study’s co-senior author. “If the mechanism we found is conserved in other organisms, we speculate that it may play a broader role in aging than has been previously appreciated and may provide a method to improve life span.”
These new observations provide another perspective to what was traditionally thought to be occurring during autophagy.
Autophagy is a cellular “housekeeping” process that promotes health by recycling or disposing of damaged DNA and RNA and other cellular components in a multi-step degradative process. It has been shown to be a key player in preventing aging and diseases of aging, including cancer, cardiovascular disease, diabetes and neurodegeneration. Notably, research has shown that autophagy genes are responsible for prolonged life span in a variety of long-lived organisms.
The classical explanation of how autophagy works is that the cellular “garbage” to be dealt with is sequestered in a membrane-surrounded vesicle, and ultimately delivered to lysosomes for degradation. However, Hansen, who has studied the role of autophagy in aging for most of her career, was intrigued by an accumulation of evidence that indicated that this was not the only process in which autophagy genes can function.
“There had been this growing notion over the last few years that genes in the early steps of autophagy were ‘moonlighting’ in processes outside of this classical lysosomal degradation,” she said. Additionally, while it is known that multiple autophagy genes are required for the increased life span, the tissue-specific roles of specific autophagy genes are not well defined.
To comprehensively investigate the role that autophagy genes play in neurons—a key cell type for neurodegenerative diseases—the team analyzed Caenorhabditis elegans, a tiny worm that is frequently used to model the genetics of aging and which has a very well-studied nervous system. The researchers specifically inhibited autophagy genes functioning at each step of the process in the neurons of the animals, and found that neuronal inhibition of early-acting, but not late-acting, autophagy genes, extended life span. These initial observations were made in Dr. Hansen’s lab at Sanford Burnham Prebys in La Jolla, California, before she moved to the Buck Institute in 2021.
An unexpected aspect was that this life span extension was accompanied by a reduction in aggregated protein in the neurons (an increase is associated with Huntington’s disease, for example), and an increase in the formation of so-called exophers. These giant vesicles extruded from neurons were identified in 2017 by Dr. Monica Driscoll, a collaborator and professor at Rutgers University.
“Exophers are thought to be essentially another cellular garbage disposal method, a mega-bag of trash,” said Dr. Caroline Kumsta, co-senior author and assistant professor at SBP. “When there is either too much trash accumulating in neurons, or when the normal ‘in-house’ garbage disposal system is broken, the cellular waste is then being thrown out in these exophers.”
Interestingly, worms that formed exophers had reduced protein aggregation and lived significantly longer. This finding suggests a link between this process of this massive disposal event to overall health, said Kumsta. The team found that this process was dependent on a protein called ATG-16.2.
The study identified several new functions for the autophagy protein ATG-16.2, including in exopher formation and life span determination, which led the team to speculate that this protein plays a nontraditional and unexpected role in the aging process. If this same mechanism is operating in other organisms, it may provide a method of manipulating autophagy genes to improve neuronal health and increase life span.
“But first we have to learn more—especially how ATG-16.2 is regulated and whether it is relevant in a broader sense, in other tissues and other species,” Hansen said. The Hansen and Kumsta teams are planning on following up with a number of longevity models, including nematodes, mammalian cell cultures, human blood and mice.
“Learning if there are multiple functions around autophagy genes like ATG-16.2 is going to be super important in developing potential therapies,” Kumsta said. “It is currently very basic biology, but that is where we are in terms of knowing what those genes do.”
The traditional explanation that aging and autophagy are linked because of lysosomal degradation may need to expand to include additional pathways, which would have to be targeted differently to address the diseases and the problems that are associated with that. “It will be important to know either way,” Hansen said. “The implications of such additional functions may hold a potential paradigm shift.”
AbstractSo how are creationists going to resolve these paradoxes? Were we designed to die before 'death entered the world', in which case 'The Fall' was part of the plan, or was that added later in a post-Fall upgrade, and did that method of ensuring we died have to depend on the failure of a system designed to clean up the mess made by poorly designed processes? In which case, why was that needed if we were designed by an omniscient, omnipotent, perfect god who originally intended us to live forever?
While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, except atg-16.2, increased lifespan, and decreased neuronal PolyQ aggregates, independently of autophagosomal degradation. Neurons can secrete protein aggregates via vesicles called exophers. Inhibiting neuronal early-acting autophagy genes, except atg-16.2, increased exopher formation and exopher events extended lifespan, suggesting exophers promote organismal fitness. Lifespan extension, reduction in PolyQ aggregates and increase in exophers were absent in atg-16.2 null mutants, and restored by full-length ATG-16.2 expression in neurons, but not by ATG-16.2 lacking its WD40 domain, which mediates noncanonical functions in mammalian systems. We discovered a neuronal role for C. elegans ATG-16.2 and its WD40 domain in lifespan, proteostasis and exopher biogenesis. Our findings suggest noncanonical functions for select autophagy genes in both exopher formation and in aging.
Yang, Y., Arnold, M.L., Lange, C.M. et al.
Autophagy protein ATG-16.2 and its WD40 domain mediate the beneficial effects of inhibiting early-acting autophagy genes in C. elegans neurons.
Nat Aging (2024). https://doi.org/10.1038/s43587-023-00548-1
© 2024 Springer Nature Ltd.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.
And was our immune system in the original design, in which case the designer was planning for pathogens and parasites, or was that added as part of the post-Fall upgrade for which the designer failed to anticipate the need?
Or will creationists use the usual tactics of either pretending to be too stupid to understand the paradoxes or simply looking the other way and pretending not to notice them?
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