Comments for Fight Aging!

Comment on Removing the Pressure of Impending Death by A. Sharafi

A. Sharafi — Wed, 31 Dec 2025 22:37:15 +0000

. . . and the firecrackers and fireworks start sounding again. People celebrating that the end is coming closer.
People do not seem to realize that the passage of time is an enemy.

Comment on Repurposing the Normal Clearance of Dead Cells to Target Unwanted Live Cells by Crescencio Batara

Crescencio Batara — Mon, 29 Dec 2025 20:29:06 +0000

My wife recently had undergone removal of her left breast due to cancer. Her Oncologist told she must undergo chemotherapy to prevent the spread of cancer iin her body. Is there other options to follow for her to avoid choteraphy

Comment on A Prodrug to Trigger Ferroptosis Based Cell Death in Senescent Cells by Edward F Greenberg

Edward F Greenberg — Sun, 28 Dec 2025 14:17:47 +0000

This seems to be a clever "EITHER/OR" dual senolytic approach if I read this correctly, targeting: 1) SA-b-gal-high cells by inducing high ROS; 2) ferritin-high/dependent cells by inducing ferroptosis. The drug could work in cells with extremely high levels of either SA-b-gal or ferritin, but could be particularly active in cells containing both (e.g., senescent cells). It aligns nicely with earlier work showing ferritin upregulation and ferroptosis sensitivity across SC subtypes, and the in vivo validation in aged mice looks promising. Thanks for sharing!

Comment on A Prodrug to Trigger Ferroptosis Based Cell Death in Senescent Cells by Dalis Dobrota

Dalis Dobrota — Sun, 28 Dec 2025 00:11:55 +0000

The authors of the article do not understand at all why senescent cells accumulate with age. Of course, it is good to remove senescent cells that hinder young cells in their work. But it is even better to slow down the formation of other senescent cells. They are hiding from us the reason why senescent cells are formed and how to reduce their number by 2 thirds. .

Comment on An Overview of Current Understanding of the Link Between Periodontal Disease and Atherosclerosis by Lee

Lee — Sat, 27 Dec 2025 15:00:47 +0000

Both are the result of immune dysfunction caused by elevated TGF beta.

Comment on Considering the Consequences of the Aging of the Pineal Gland by Zeeker

Zeeker — Fri, 26 Dec 2025 23:59:47 +0000

You wrote: ''We live in a strange world populated by strange people.'' Well said!

Comment on A Discussion of the Biochemistry of Cardiac Fibrosis by Lee

Lee — Fri, 26 Dec 2025 16:23:51 +0000

New Conboy paper

Propanolol increases oxytocin
Pentoxifylline reduces TGF beta and JAK/STAT

"In Old Mice, Exercise Induces Inflammation and Fibrosis Unless Alk5-Inhibitor and Oxytocin Are Used"
Exercise and diet are the best-known methods for attenuating aging-related health decline. However, exercise in older age has diminished gains of strength and agility, and a danger of unrepaired muscle damage. Improving the understanding of age-related differences in response to exercise, our results demonstrate that in old mice, downhill treadmill (eccentric) exercise causes increased influx of CD45+ cells (inflammation) and fibrotic index (fibrosis) in the heart and skeletal muscles. To explain these changes, we identified newly synthesized proteins through bio-orthogonal noncanonical amino acid tagging (BONCAT) and established that exercise exacerbated age-associated protein patterns through a dysregulated transforming growth factor (TGF)-β, Ras/MAPK/PI3Akt, and JAK/STAT pathways. Testing causality, we found that an inhibitor of TGF-β (Alk5 inhibitor, A5i) in combination with the age-diminished peptide oxytocin, previously shown to rejuvenate muscle and brain in sedentary animals, allowed aged mice to exercise without pathologies of skeletal and heart muscles and youthfully restored their de novo proteomes.

https://pubmed.ncbi.nlm.nih.gov/40536399/

Comment on Targeting TGFβ to Treat Fibrotic Disease by Lee

Lee — Fri, 26 Dec 2025 13:37:50 +0000

I saw this post when it was new and didn't fully understand the implications.

TGF beta along with IL-10 are hugely immune suppressive and upregulate all of the immune checkpoints causing age related immune dysfunction. If you can reduce IL-10 and TGF over time the elevated checkpoints has no stimulus keeping them on and they will reduce on their own.

You can measure IL-10 and TGF beta1 for less than $100 each with a doctor's order through Labcorp.

The active form of TGF beta is the one that actually matters but there isn't a practical way to measure it so you just have to live with the latent form measurement of TGFB1. There are papers showing the processing of the blood sample can give wide variations in the results almost to the point of meaninglessness so beware.

My own IL-10 and TGFB1 measured very high and I have less than ideal immune function and my facial and whole body fat has declined. I reduced my IL-10 with metoprolol and/or atovaquone. I will remeasure TGFB1 in a few weeks.

My pirfenidone is on order and in the meantime i'm doing a combination of pentoxifylline, metformin, valsartan/sacubatril and propanolol. My face got fatter in a good way in days but it is way too early to call this a win.

There is elevated cancer risk with pioglitazone so beware.

Comment on Lipofuscin, an Overlooked Contributing Cause of Neurodegeneration by Reason

Reason — Tue, 23 Dec 2025 03:40:03 +0000

In reply to erasmus. @erasmus: No, 7-ketocholesterol is in another category.

Comment on Lipofuscin, an Overlooked Contributing Cause of Neurodegeneration by erasmus

erasmus — Mon, 22 Dec 2025 22:48:48 +0000

would 7kc be classified as lipofuscin?