The ultimate plan to live forever is a brand new body.
Category: life extension
Aging Can be Slowed Down
Scientists are studying a protein called HMGB1 that’s released by damaged or stressed cells and can trigger inflammation in nearby healthy cells, accelerating the aging process. If this research holds up, it could completely change how we think about aging and disease.
How stimulating the vagus nerve could protect the brain from Alzheimer’s disease
Developing tau tangles doesn’t mean a person has Alzheimer’s disease – in fact, it happens to nearly everyone to varying degrees. But because these changes start in the locus coeruleus, some brain researchers – myself included – see this area as a canary in the coal mine for developing Alzheimer’s disease.
We are exploring whether stopping or slowing down tau tangles in this brain region, or otherwise maintaining its health, may be a way to interrupt how the disease ultimately unfolds and to prevent other aspects of cognitive aging.
Emerging research from my lab and others is investigating the idea that a therapy called vagus nerve stimulation, which is already widely used for other health conditions, could be one way of keeping the locus coeruleus functioning properly.
Longevity Isn’t Equal: Why Life-Extending Treatments May Be a “Biological Lottery”
Extending life is only part of the goal in aging research. Scientists also want more people to reach old age in good health, with fewer differences in when individuals die. This ideal outcome is often described as “squaring the survival curve,” where most deaths are pushed into a narrow window late in life rather than spread out across many years.
To test how close current science comes to that goal, University of Sydney researchers revisited a large meta-analysis of studies in vertebrates. They focused on three widely studied interventions: dietary restriction, rapamycin, and metformin. While all are linked to longevity, they work in different ways.
Dietary restriction involves reducing calorie intake without causing malnutrition. It has been known for more than a century to extend lifespan in animals and is thought to act in part by dialing down a key cellular growth pathway called mTORC1, which helps regulate metabolism and aging. Because strict diets are difficult to maintain, scientists have searched for drugs that mimic these effects. Rapamycin directly blocks mTORC1 activity, while metformin, a common diabetes medication, influences the same pathway indirectly by altering how cells sense energy levels.
Molecular Markers of Blood Cell Populations Can Help Estimate Aging of the Immune System
Aging of the immune system involves functional changes in individual cell populations, in hematopoietic tissues and at the systemic level. They are mediated by factors produced by circulating cells, niche cells, and at the systemic level. Age-related alterations in the microenvironment of the bone marrow and thymus cause a decrease in the production of naive immune cells and functional immunodeficiencies. Another result of aging and reduced tissue immune surveillance is the accumulation of senescent cells. Some viral infections deplete adaptive immune cells, increasing the risk of autoimmune and immunodeficiency conditions, leading to a general degradation in the specificity and effectiveness of the immune system in old age.
Consistently Higher HRV, Lower RHR Since 2018
Join us on Patreon! / michaellustgartenphd.
Discount Links/Affiliates:
Blood testing (where I get the majority of my labs): https://www.ultalabtests.com/partners… Metabolomics: https://www.iollo.com?ref=michael-lus… Use Code: CONQUERAGING At Checkout Clearly Filtered Water Filter: https://get.aspr.app/SHoPY Epigenetic, Telomere Testing: https://trudiagnostic.com/?irclickid=… Use Code: CONQUERAGING NAD+ Quantification: https://www.jinfiniti.com/intracellul… Use Code: ConquerAging At Checkout Oral Microbiome: https://www.bristlehealth.com/?ref=mi… Enter Code: ConquerAging SiphoxHealth Blood Testing (ApoB, GrimAge): https://siphoxhealth.com/mlustgarten Green Tea: https://www.ochaandco.com/?ref=fqbtflod Use Code: ML10OFF Diet Tracking: https://shareasale.com/r.cfm?b=139013… If you’d like to support the channel, you can do that with the website, Buy Me A Coffee: https://www.buymeacoffee.com/mlhnrca Conquer Aging Or Die Trying Merch! https://my-store-d4e7df.creator-sprin…
Blood Testing Essentials (Biological Age, CVD-Risk, Kidney Health and Function):
PhenoAge (Biological Age): https://www.ultalabtests.com/partners…
Risk-weighted ApoB (a better CVD predictor than LDL, non-HDL cholesterol, and ApoB): https://www.ultalabtests.com/partners…
Kidney health and function: https://www.ultalabtests.com/partners…
At-Home Metabolomics: https://www.iollo.com?ref=michael-lus…
Tomatidine is a senotherapeutic compound that improves cognitive function and reduces cellular senescence in aged mice
Cellular senescence drives aging and age-related dysfunction across multiple tissues, including the brain. Through a high-content, senescent cell-based phenotypic screen of a small panel of natural products, we identified tomatidine, an aglycone of tomatine found in tomatoes, as a previously unrecognized senotherapeutic agent. In senescent human brain microvascular endothelial cells and fibroblasts, tomatidine selectively suppressed SASP expression without affecting p16Ink4a or p21Cip1 levels consistent with a senomorphic effect. In aged mice, tomatidine reduced frailty and improved motor coordination and cognitive performance. These functional benefits were accompanied by reduced senescence markers (p16 Ink4a, p21 Cip1, and telomere-associated DNA damage foci) in liver, skin, and hippocampal neurons, along with decreased neuroinflammation and microglial activation. Tomatidine also diminished brain endothelial cell senescence while enhancing tight junction protein expression, suggesting preserved blood–brain barrier integrity. Together, these findings identify tomatidine as a promising senescence-targeting compound with beneficial effects in aged mice and support its further evaluation in mechanistic and translational studies.
Body-wide multi-omic counteraction of aging with GLP-1R agonism
Online now: Body-wide multi-omic counteraction of aging with GLP-1R agonism: (Cell Metabolism 37, 2362–2380.e1–e8; December 2, 2025)
Online now: (Cell Metabolism 37, 2362–2380.e1–e8; December 2, 2025)
Following publication, Steve Horvath and colleagues at the Clock Foundation alerted us to a platemap error in the DNA methylation (DNAm) data. Our investigation pinpointed the potential source of this error. We provided samples on 96-well plates in a row-wise orientation instead of the column-wise orientation specified in the Clock Foundation’s protocol. Subsequently, incorrect assignment of metadata for 36 samples (out of 459) that contributed data to the paper likely occurred during the transposition and rearrangement of a subset of samples on two incompletely filled plates prior to the assay. Working with Clock Foundation colleagues, we have corrected the metadata for 33 samples and discarded 3 samples for which we could not retrieve the metadata with total certainty.
This error impacted DNAm data for the following tissues: