Bottlenecks of Aging by the Amaranth Foundation

Executive Summary

By 2029, the United States will spend $3 trillion dollars every year — half its federal budget — on adults aged 65 and older. By the same year, nearly 20 million Americans will die from age-related illnesses. Yet research on the biology of aging remains overlooked. Despite a 70-fold increase in funding for aging research since the last decade, the incentives of governments and for-profit investment do not always lend themselves to early bets on ambitious science or field-building. Amaranth is committed to filling this gap by funding moonshot approaches to longevity while expanding the field’s talent pool.

In 2022, the Amaranth Advisory Board — a group of leading experts in longevity and neuroscience — convened to address the bottlenecks hindering progress in extending healthy human lifespan. During the meeting, the group enumerated focus areas that require philanthropic investment. Over the last two years (2021-2023), we’ve directed over $30M of funding to scientific labs, policy-makers, educational initiatives, and prize funding to further the most promising research in these overlooked areas.

Below, we outline initiatives which, if executed, could meaningfully accelerate the advancement of aging science and other life-extending technologies. The resulting document is a philanthropic menu, for which Amaranth is seeking both talent to execute on and co-funders. If you are a founder, researcher, or philanthropist interested in executing or co-sponsoring one or several of the projects or proposals below, please reach out to us here, or submit a research proposal here.

Executive Summary
Priority #1: Accelerating the path to market for aging drugs
Priority #2: Understanding the aging brain
Priority #3: Replacing damaged tissues and organs
Priority #4: Activating talent
Priority #5: Advancing biopreservation technology
Priority #6: Additional therapeutic targets to extend lifespan
Priority #7: Increased in aged models to study longevity and disease
Priority #8: Characterizing age-related damage accumulation
Priority #9: Deciphering mechanisms of germline immortality
Priority #10: Applying new tools towards fundamental problems in aging
Priority #11: Forging new narratives for aging
Priority #12: Economic data collection and analysis


#9 Germline immortality IMO is not as described. Germline cells are not active cells. As DNA is vulnerable when being transcribed inactive cells have less vulnerable DNA. That does not imply germline immortality. If the germline is mutated then it might end at the embryonic stage.

Did you read the full entry?

Priority #9

Deciphering mechanisms of germline immortality

Our germ cells - sperm and egg cells - are continuations of a lineage billions of years old. A better understanding of how these cells resist the aging process could be the key to unlocking true rejuvenation.

Active Projects

We don’t yet know how to prevent our bodies from aging. However, a subset of our cells have effectively already solved the problem of damage accumulation. Germ cells naturally reset damage and rejuvenate through the process of fertilization and development. Egg cells, for instance, can clear out toxic protein aggregates before they mature, preventing them from being passed on. This regenerative capability means germline cells have persisted for billions of years without succumbing to the damage that normally shuts down old cells. As a result, old germ cells can spawn young animals and keep biological lineages going indefinitely.

Deciphering the mechanisms of germ cell rejuvenation and how to apply them throughout the body is a promising path. Yet germline immortality remains overlooked. To unlock novel rejuvenation techniques, we must nurture and expand the scientific subfields which possess the potential to translate rejuvenation into humans, including germline rejuvenation and rejuvenation screening approaches.

Research We’ve Funded

  1. Proteome rejuvenation in vertebrate oocytes - germline reset in Xenopus frogs (Harvard)

Recommendations for Proposals and Funders

  1. Field building with an annual seminar to connect researchers in a small nascent field, or workshop to roadmap biggest unanswered questions regarding germline rejuvenation. Some unanswered questions include the below:
  2. Understanding current mechanisms of germline rejuvenation (e.g. by gamete formation).
  3. Rejuvenation vs. clonal selection (e.g. resistance to decline or active rejuvenation).
  4. Consequences of failure to rejuvenate or clonally select (e.g. unviable oocytes, germline aging, fertility).
  5. Funding grants for basic research to study the mechanisms of germline rejuvenation.
  6. Screening for transcription-factor based rejuvenation, chemical reprogramming, and protein reprogramming in germline model systems.
1 Like

I didn’t read the original document, but I did read the words “germline immortality”.

That does not mean what I said was wrong.

If the germline has mutated such that it is not viable we won’t see it.

I think you and they are talking about slightly different things - thats all.

I don’t think we are. There is a good question as to why germline DNA appears to be less likely to be mutated. That IMO is because the cells are less active.

However, as to why the germline today functions after eons of replication. That is survivorship bias.