Eric, the convergence of thymic involution with inflammaging mechanisms is the key insight here. Especially that obesity, chronic stress, and smoking drive thymic adipocyte infiltration through systemic inflammation.
What's underappreciated IMO: chronic indoor environments feed that same pathway.
Americans spend 93% of life indoors, where circadian disruption, elevated CO2, and reduced phytoncide exposure independently upregulate inflammatory cascades. Just 20 minutes outdoors reduces cortisol 21% (Hunter et al., 2019), which is a behavioral lever most people never pull.
That 73% wanting their thymic score in your poll, with 600 votes as of now, tells me some patients are ready. The first intervention may be environmental, not pharmaceutical.
I expand on this in a new book Indoor Epidemic: more on indoorepidemic,com, where there's a short version of Outdoor Rx for 7 days free, a cheat sheet and other resources.
If RANK & its ligand (RANKL) are considered key regulators of medullary TECs, would an observational study with patients given denosumab (bone development modulator) discover changed in their thymus gland?
Such a study would however not be gender neutral given it's my observation primarily it's offered to women. This being said, men receive the drug as an adjunct therapy for prostate cancer.
Interestingly the heterochronic parabiosis experiments dont find naive T cells from the young participant invading the thymus of the old participant. This suggests those youthful hormones/growth factors alone arent sufficient to regenerate the thymus. But TEC engraftment seems to work like gangbusters.
There is another biological process associated with thymic involution, pregnancy. But there we see this innate postpartum reversal marked by you guessed it resident TEC proliferation.
My questions. Can a similar AI model predict problematic pregnancies from thymic CTs and conversely could a model learn the hallmarks of innate thymic rejuvenation by studying the postpartum reversal images?
Fascinating stuff, clearly explained (as usual). What's not so clear is what to do about it. I've been incubating a self-serving theory that obesity per se is not the problem. The problem may be some of the associated metabolic changes associated with obesity. One of these is elevated blood glucose and insulin levels. I posit that this is the common final pathway between overeating/unwise eating and increases in mortality from multiple sources. The implications are important. For example, if SUGAR is the fundamental problem, then LDL and other metabolic consequences of unwise diet may be of secondary importance. I know big pharma makes a lot of money from various treatments aimed at preventing/reducing obesity, and that they plow a fair amount into research studies that never really address whether sugar might be the basic link. I've personally struggled mightily with adverse effects of lipid lowering agents, including a simultaneous tear of both quadriceps tendons and several more minor but still crippling consequences such as the tendon detachments in both gluteus muscles that kept me from exercising all last year. My cardiologists, who seem well-qualified, haven't been able to suggest anything better than more trials of more expensive lipid-lowering agents that aren't supposed to bother most users but have uniformly distressed me. I realize this isn't the most common picture, but it's had a massive impact on my happiness over the past couple of decades so I'm looking for a better answers. I'm still "overweight" but no longer obese, having shed the Type II diabetes through dietary discipline, so I can't help wondering if I should be spending nearly $600/month for evolocumab. So if anybody can clarify this for me, you'll be helping a lot of folks!
Eric, the convergence of thymic involution with inflammaging mechanisms is the key insight here. Especially that obesity, chronic stress, and smoking drive thymic adipocyte infiltration through systemic inflammation.
What's underappreciated IMO: chronic indoor environments feed that same pathway.
Americans spend 93% of life indoors, where circadian disruption, elevated CO2, and reduced phytoncide exposure independently upregulate inflammatory cascades. Just 20 minutes outdoors reduces cortisol 21% (Hunter et al., 2019), which is a behavioral lever most people never pull.
That 73% wanting their thymic score in your poll, with 600 votes as of now, tells me some patients are ready. The first intervention may be environmental, not pharmaceutical.
thanks very much for your input, John!
I expand on this in a new book Indoor Epidemic: more on indoorepidemic,com, where there's a short version of Outdoor Rx for 7 days free, a cheat sheet and other resources.
If RANK & its ligand (RANKL) are considered key regulators of medullary TECs, would an observational study with patients given denosumab (bone development modulator) discover changed in their thymus gland?
Such a study would however not be gender neutral given it's my observation primarily it's offered to women. This being said, men receive the drug as an adjunct therapy for prostate cancer.
JJF Phm 🇨🇦 p.s. mostly a curious thought
Certainly worth probing. Thanks
Interestingly the heterochronic parabiosis experiments dont find naive T cells from the young participant invading the thymus of the old participant. This suggests those youthful hormones/growth factors alone arent sufficient to regenerate the thymus. But TEC engraftment seems to work like gangbusters.
There is another biological process associated with thymic involution, pregnancy. But there we see this innate postpartum reversal marked by you guessed it resident TEC proliferation.
My questions. Can a similar AI model predict problematic pregnancies from thymic CTs and conversely could a model learn the hallmarks of innate thymic rejuvenation by studying the postpartum reversal images?
Good question. Not clear but would be interesting to see if effects of thymic health are modulated by pregnancy
Fascinating stuff, clearly explained (as usual). What's not so clear is what to do about it. I've been incubating a self-serving theory that obesity per se is not the problem. The problem may be some of the associated metabolic changes associated with obesity. One of these is elevated blood glucose and insulin levels. I posit that this is the common final pathway between overeating/unwise eating and increases in mortality from multiple sources. The implications are important. For example, if SUGAR is the fundamental problem, then LDL and other metabolic consequences of unwise diet may be of secondary importance. I know big pharma makes a lot of money from various treatments aimed at preventing/reducing obesity, and that they plow a fair amount into research studies that never really address whether sugar might be the basic link. I've personally struggled mightily with adverse effects of lipid lowering agents, including a simultaneous tear of both quadriceps tendons and several more minor but still crippling consequences such as the tendon detachments in both gluteus muscles that kept me from exercising all last year. My cardiologists, who seem well-qualified, haven't been able to suggest anything better than more trials of more expensive lipid-lowering agents that aren't supposed to bother most users but have uniformly distressed me. I realize this isn't the most common picture, but it's had a massive impact on my happiness over the past couple of decades so I'm looking for a better answers. I'm still "overweight" but no longer obese, having shed the Type II diabetes through dietary discipline, so I can't help wondering if I should be spending nearly $600/month for evolocumab. So if anybody can clarify this for me, you'll be helping a lot of folks!