Thanks for the summary! A cautionary note: You shouldn't say "upregulated" and "downregulated" unless there is actually evidence that a gene is upregulated or downregulated.
First, you can't actually measure gene expression for all genes at once with current tech; you can only measure the abundance of their mRNA (as the study at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240505 did), which is not always proportional to protein abundance. If a cell is simultaneously expressing mRNA for a gene, and hairpin RNA directed against that mRNA, the level of gene expression will be less than that suggested by the mRNA abundance. The same thing will happen if the cell is simultaneously producing a protein, and another protein that breaks down that first protein. (Your muscle cells do this all the time; they're always fighting internally between one gang that wants to build more muscle, and another that wants to tear it down.) Increased mRNA may be a symptom of increasing disagreement between genes. Such dysfunctions of gene regulation certainly occur with aging. Also, ribosomes are proteins, and like other proteins, they're less-effective with age, so the same mRNA expression in an old animal won't produce as much protein. Proteins with unusual amino acids, or ones the organism is low on at present, are often expressed at lower levels.
Second, a protein's abundance isn't necessarily proportional to its activity. /Lots/ of protein modifications go on continually that up-regulate or down-regulate protein activity, and these don't show up on an RNA microarray. Aged proteins, and proteins produced by aged animals, are both more-likely to have lower activity due to damage to protein or DNA. And as the cell fills up with enlarged liposomes and protein aggregates, and the cytoskeletal transport system ages, and mitochondrial dysfunction increases, the rate at which partner proteins can find each other, and the energy available to do anything when they find each other, will change, changing the effective activity level.
But most-importantly, when aging researchers find that a protein's mRNA expression or protein concentration is increased with age, they usually assume that it is "upregulated" (meaning the organism "decides" to increase that protein's concentration) to combat effects of aging if that fits their theory. They assume that it's a waste product (if it's a protein) or the result of dysregulation upstream to it (if they're measuring mRNA), and that it's /causing/ the effects of aging, if that fits their theory. For example, you've all heard that cholesterol causes atherosclerosis; but the evidence is correlational. Experiments trying to link higher cholesterol intake to higher atherosclerosis mostly fail, or fail outside a narrow range of intake. Unless things have changed recently, some researchers believe cholesterol production is up-regulated to fight atherosclerosis.
Better to say "increased mRNA" and "decreased mRNA", or at least "increased expression" and "decreased expression" (which is not technically merited, but is less-misleading than "upregulated" and "downregulated").
Thanks for the summary! A cautionary note: You shouldn't say "upregulated" and "downregulated" unless there is actually evidence that a gene is upregulated or downregulated.
First, you can't actually measure gene expression for all genes at once with current tech; you can only measure the abundance of their mRNA (as the study at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240505 did), which is not always proportional to protein abundance. If a cell is simultaneously expressing mRNA for a gene, and hairpin RNA directed against that mRNA, the level of gene expression will be less than that suggested by the mRNA abundance. The same thing will happen if the cell is simultaneously producing a protein, and another protein that breaks down that first protein. (Your muscle cells do this all the time; they're always fighting internally between one gang that wants to build more muscle, and another that wants to tear it down.) Increased mRNA may be a symptom of increasing disagreement between genes. Such dysfunctions of gene regulation certainly occur with aging. Also, ribosomes are proteins, and like other proteins, they're less-effective with age, so the same mRNA expression in an old animal won't produce as much protein. Proteins with unusual amino acids, or ones the organism is low on at present, are often expressed at lower levels.
Second, a protein's abundance isn't necessarily proportional to its activity. /Lots/ of protein modifications go on continually that up-regulate or down-regulate protein activity, and these don't show up on an RNA microarray. Aged proteins, and proteins produced by aged animals, are both more-likely to have lower activity due to damage to protein or DNA. And as the cell fills up with enlarged liposomes and protein aggregates, and the cytoskeletal transport system ages, and mitochondrial dysfunction increases, the rate at which partner proteins can find each other, and the energy available to do anything when they find each other, will change, changing the effective activity level.
But most-importantly, when aging researchers find that a protein's mRNA expression or protein concentration is increased with age, they usually assume that it is "upregulated" (meaning the organism "decides" to increase that protein's concentration) to combat effects of aging if that fits their theory. They assume that it's a waste product (if it's a protein) or the result of dysregulation upstream to it (if they're measuring mRNA), and that it's /causing/ the effects of aging, if that fits their theory. For example, you've all heard that cholesterol causes atherosclerosis; but the evidence is correlational. Experiments trying to link higher cholesterol intake to higher atherosclerosis mostly fail, or fail outside a narrow range of intake. Unless things have changed recently, some researchers believe cholesterol production is up-regulated to fight atherosclerosis.
Better to say "increased mRNA" and "decreased mRNA", or at least "increased expression" and "decreased expression" (which is not technically merited, but is less-misleading than "upregulated" and "downregulated").
There's a failed LaTeX expression at the end of this post?