Ageing

Both descriptive and prescriptive

January 11, 2022 — January 21, 2025

drugs
faster pussycat
fit
gene
health
mind
Figure 1

General theory of ageing and avoiding it. Placeholder.

See also biomarkers.

Lifespan/healthspan/ageing is not my area of research. I’m not qualified to assess in specific detail the outlandish claims made by snake-oil sellers since I do not know how biology works. I am not triaging the literature review high enough on my list. That said, I can assess crap statistics and bad reasoning well enough to report that it is sometimes tedious.

There is a danger of pseudoscience and quackery in this area, so beware. The incentives are clearly not great: since cashed-up older people rarely want to die, selling them small trials with marginal benefits and low reproducibility is a lucrative enough business to prop up a lot of bad science indefinitely.

Which interventions make us live healthier longer?

Quantified self/nutrition etc. for lifespan extension. Probably best read in concert with biomarker tracking.

Figure 2

1 Sirtuin stuff

As seen in Sinclair (2021), who recommends taking various supplements that affect the sirtuin pathway, whatever that is.

Berberine, resveratrol, metformin, NAD+ precursors, fasting, etc.

See also

More metformin stuff:

I’m interested in the observation that fasting also benefits the immune system. It seems to work in mice (Brandhorst et al. 2024).

2 GlyNAC

This is also on the podcastosphere.

“Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial” (Kumar et al. 2023)

3 Blood plasma dilution

Blood boys etc.

Or do you even need blood boys?

See this Open Philanthropy summary:

The challenge: Given the central role ageing plays in disease progression, a better understanding of the ageing process could lead to improvements in a broad range of health outcomes.

The research: Dr. Irina Conboy, a professor in the Department of Bioengineering at UC Berkeley, has made significant strides in the scientific understanding of how blood factors—hormones, proteins, and other molecules circulating in the bloodstream—influence ageing. Though Dr. Conboy’s work had already gained recognition by the time of our first grant in 2017, we believed it was still neglected relative to its potential in a field that had received much private investment but little public research funding.

With support from our team and other funders, Dr. Conboy:

  • Developed micro-apheresis for mice, an innovative technique that allows filtration of blood to remove small molecules.
  • Identified 10 novel biomarkers of ageing.
  • Uncovered a major mechanism for rejuvenation through modulation of the TLR4 receptor, which appears to play a key role in age-related inflammation.
  • Revealed (Kim et al. 2022) that diluting old blood (with saline and purified albumin (Yilmaz et al. 2011)) — rather than adding young blood, which has garnered provocative headlines—can have rejuvenating effects on muscle, liver, and brain tissue.

The impact: Dr. Conboy’s research offers a new perspective on how factors in blood affect ageing. Her findings suggest that identifying and counteracting pro-ageing factors in blood could potentially slow or reverse certain effects of ageing, opening new avenues for improving human health and longevity.

4 What biomarkers are cheap to track to assess the effectiveness of ageing interventions?

TODO

5 Collagen

Why would collagen supplementation (some sources recommend a protocol with vitamin C and exercise) help with collagen production? It all gets digested, right? Some small studies suggest eating collagen is nonetheless good for collagen production (Czajka et al. 2018; DePhillipo et al. 2018; Shaw et al. 2017). I would like a meta-analysis and some extra data.

6 Alternatives

Death.

7 Incoming

8 References

Attia, and Gifford. 2023. Outlive: The Science and Art of Longevity.
Brandhorst, Levine, Wei, et al. 2024. Fasting-Mimicking Diet Causes Hepatic and Blood Markers Changes Indicating Reduced Biological Age and Disease Risk.” Nature Communications.
Campbell, Bellman, Stephenson, et al. 2017. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis.” Ageing Research Reviews.
Czajka, Kania, Genovese, et al. 2018. Daily Oral Supplementation with Collagen Peptides Combined with Vitamins and Other Bioactive Compounds Improves Skin Elasticity and Has a Beneficial Effect on Joint and General Wellbeing.” Nutrition Research.
DePhillipo, Aman, Kennedy, et al. 2018. Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review.” Orthopaedic Journal of Sports Medicine.
Kim, Kiprov, Luellen, et al. 2022. Old Plasma Dilution Reduces Human Biological Age: A Clinical Study.” GeroScience.
Kulkarni, Brutsaert, Anghel, et al. 2018. Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults.” Aging Cell.
Kulkarni, Gubbi, and Barzilai. 2020. Benefits of Metformin in Attenuating the Hallmarks of Aging.” Cell Metabolism.
Kumar, Liu, Suliburk, et al. 2023. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial.” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences.
Mohammed, Hollenberg, Ding, et al. 2021. A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan.” Frontiers in Endocrinology.
Shaw, Lee-Barthel, Ross, et al. 2017. Vitamin C–Enriched Gelatin Supplementation Before Intermittent Activity Augments Collagen Synthesis.” The American Journal of Clinical Nutrition.
Sinclair. 2021. Lifespan: Why We Age — and Why We Don’t Have To.
Yilmaz, Can, Oral, et al. 2011. Therapeutic plasma exchange in an intensive care unit (ICU): a 10-year, single-center experience.” Transfusion and Apheresis Science: Official Journal of the World Apheresis Association: Official Journal of the European Society for Haemapheresis.
Younes, Al-Hasan, Eldos, et al. 2017. Assessment of Quality Control Parameters and in Vitro Bioequivalence/Interchangeability of Multisourced Marketed Metformin Hydrochloride Tablets.” Qatar Medical Journal.
Zhu, Yoshida, Tsuboi, et al. 2021. Quality and Authenticity of Metformin Tablets Circulating on Japanese Websites.” Therapeutic Innovation & Regulatory Science.