Thank you for your contributions to the Future of Longevity Impact Roadmap! The discussions in this community have helped XPRIZE understand the challenges that need to be overcome to extend human lifespans and identify potential breakthroughs in longevity.

The Impact Roadmap is now complete. You can browse the interactive version on the XPRIZE website and download the full report.

The discussion forums about obstacles to long life, innovations in life extension and breakthroughs in longevity will be closed, but alumni of this project are invited to join the Future of Longevity Group to continue the conversation and stay in touch.

Aging, Figured Out

XPRIZEXPRIZE Los Angeles, CaliforniaPosts: 116 admin
Outcome

A theory of aging that ties together all the different mechanisms of aging and explains the relationship between them in a quantifiable way. The model will predict how any change of the involved factors will affect the aging process.

Why the Need?

There’s currently no unified theory of aging that explains how the mechanisms of aging influence each other, the body, and the aging process. Without such a theory, attempts to significantly slow down or even reverse aging retain high risks of unknown negative side effects and dead-end research. A unified theory will help scientists better understand the aging process and will guide drug developers and biomedical engineers in their attempts to slow down or reverse aging.

Stipulations for a Successful Breakthrough Solution
  • The unified model must tie together all known mechanisms of aging, or explain why some are left out
  • The unified model must be explainable and quantifiable, so that it can be used to predict future occurrences and the result of any intervention
  • The unified model does not have to describe human aging, but the more advanced the animal it describes is, the better.

Promising Technologies for Solutions

It is likely that the creation of such a theory will require the use of sophisticated artificial intelligence and machine learning engines, as well as insights gained from the world’s longevity and aging researchers.

Expected year for proof of concept: 2030
Expected year for mass-scaling: 2040

Comments

  • SamBlakeSamBlake Los Angeles, CaliforniaPosts: 34 mod
    Do you think SENS or Hallmarks of Aging are enough? What are their shortcomings?
  • NickOttensNickOttens Barcelona, SpainPosts: 396 admin
    @mkaeberlein, @MSK, @Jay, what do you think?
  • MSKMSK Posts: 1
    Just a few very short comments.
    1) I think, like most people in the field, that a unified theory of aging is unlikely to exist. To give you another way to think of this:
    "Give me a unified theory for why your car breaks down"

    2) I think the hallmarks are a good guide, but I think "extracellular matrix aging" is a missing concept.
  • ymedanymedan Posts: 81 ✭✭
    There will always be a "unified theory" du jour. The longer we live, the longer the trail of theories will be (until terminated by a meteorite :-)
  • marz62marz62 Posts: 48 ✭✭
    edited May 23
    While I agree in general with the first two posters' comments/points - and I compare MSK's comment to the search for a cure for Cancer (wherein there are now numerous 'cures' [effective, life-extending treatments) for many cancers, but no one "cure" because research has revealed MANY causes for cancer, and, each cancer is unique in its gene expression profile and causal chain). However, I think the development of a standard Model of Aging (like the Standard Model of Quantum Physics) is on the not-too-distant horizon...as our theories of Aging are put to the test in laboratory and Real Life experiments (and one other key development; see last paragraph).

    The key thing that must happen -- to begin to formulate an accurate theory and model -- is to distinguish causes of Aging from ("downstream") effects of Aging. We already know that certain genes -- first discovered in Drosophila animal models -- extend lifespan under certain alterations, and, that caloric restriction extends lifespan in animals (even though the human 'analogs' of the SIRT gene and restricted calorie diet don't quite produce the same results as in non-human animals). But this research will lead, relatively soon, to an 'Animal Aging Model' (a step towards a Human Aging Model)...and from that, we will gain a predictive capability (the purpose of all animal models) that we seek.

    That said, right now, based upon my reading and archival research, we are still in the discovery phase of the Science of Aging.

    For example, recent work by Lloyd and Rothstein (2019) on neurodegenerative diseases has resulted in a fundamental finding (applicable to Aging): loss of functioning nucleocytoplasmic transport in neurons (which leads to a build-up of proteins in the cell cytoplasm and cell nucleus -- aggregates of which produce the "plaques and tangles" noted in AD, for example). The resulting diseases (like AD, FTD, Huntington's, and others) present the symptoms, like memory loss, we associate with Aging. These scientists and others are already experimenting with several drug candidates that target the pores in our cell nuclei to "unstick" this proteinaceous blockage and restore the normal functioning to out (brain) cell transport machinery.

    Other work has found cell "reactiviation" (where otherwise cells would stop dividing and die-off) as another cellular malfunction that produces cellular and organ tissue effects associated with disease and Aging (which tend to go hand in hand, right now). No doubt additional important discoveries -- and the general biological principles that underlie them -- will be made, as they are now being made almost daily.

    My point is that while we are eager to find a "unified theory" of Aging (and thereby have the means to put the "brakes" on Aging), and while others will always remain skeptical of any claim to a "cure for Aging" (aka "Fountain of Youth")...we are not yet there. But, will we be there in 5 to 10 years..? Well, with the combined efects of accelerated innovation AND the implementation and integration of Artificial Intelligence in Bio-Science (e.g., robot scientists conducting millions of automated experiments in a single day)...I think so. Definitely.

    [If anyone would like to read my 2013 (!) thought paper on this development -- the integration of AI in the Life Sciences -- please contact me and I will send you a copy]
  • NickOttensNickOttens Barcelona, SpainPosts: 396 admin
    @Elena_Milova, @DidierC, @sheesh, what are your thoughts on this potential breakthrough? Would it go a long way to achieving radical life extension?
  • ymedanymedan Posts: 81 ✭✭
    There has been a recent research published on reversing aging with fecal transplant from young mice to senior mice.... I have put the reference elsewhere in this forum.
  • NickOttensNickOttens Barcelona, SpainPosts: 396 admin
    Thanks! It's the Could boosting the gut microbiome be the secret to healthier older age? discussion, in case others are interested.
  • marz62marz62 Posts: 48 ✭✭
    edited June 6
    @ymedan @NickOttens -

    I definitely am coming to believe that maintaining a healthy microbiota (the collective of 'gut bugs' in the lower intestinal regions) is one major key to healthy aging (maintaining one's 'healthspan' as opposed to increasing only one's lifespan). So, to the extent that fecal transplant experiments (mainly in mice) support some connection (e.g., immunological) with prolonging healthy aging (diminished GI pathologies), I agree with this practice.

    However, microbes are known for their ability to 'share' DNA (via horizontal gene transfer, and, through 'lateral transduction', via bacterophages). So, given that complete genetic profiles (gene expression assays) are not being performed on these transplanted microbes, the reality is we don't know entirely what is being 'transplanted' into the recipient's GI tract in terms of new, damaged, or mutated genes.

    Just a cautionary observation.
  • ymedanymedan Posts: 81 ✭✭
    @marz62 Point well made. I have attended a dinner with folks from Nestle Health Science Institute. IMHO, they plan to be the "Monsanto" of pre/pro/biotics supplements/drugs. This is a speculation on my side but time will tell.

    Also, I expect soon a breakthru research paper on microbiome-mitchondria communication. IMHO, this is the key mechanism of aging, which may be modulated by an appropriate mitochondrial repair therapy. As I mentioned elsewhere, Mitochondrial DNA is not protected and therefore prone to errors (=mutations).
  • marz62marz62 Posts: 48 ✭✭
    edited June 6
    @ymedan
    Well that sounds exciting -- I look forward to reading the paper! And yes, mitochondrial dysfunction or malfunction (breakdown) is highly correlated with aging (via cellular function breakdown), so, it makes sense to look at mitochondria (and its repair or 'restoration') for improving healthspan or promoting healthy aging. This is the main motivator in using NAD+ (or its precursors, like NR, NMN) in an "anti-aging elixir", as NAD+ repairs/restores mitochondrial function.

    The problem is that cancer cells also depend on maintaining high NAD+ levels and proper mitochondrial function to proliferate (Zhang et al, others). Thus, there is a robust debate in the research community currently concerning NAD's role (and by association, the mitochondrion 's) in tumorigenesis, and the pro-inflammatory response, in general. Research in this area is conflicting (with some showing that inhibiting NAD+ caused DNA damage/tumorogenesis, while other studies show that inhibiting the enzymes that synthesize NAD+ kills cancer cells).

    Here is a good popular science article on the whole debate: https://www.scientificamerican.com/article/cancer-research-points-to-key-unknowns-about-popular-antiaging-supplements/
  • ymedanymedan Posts: 81 ✭✭
    @marz62
    Thanks. My gut tells me that the Mitochondria and Microbiota are talking ... and they form a "community consesus" of some sort whether to support cancer growth or not. Hence the debate.

    Is the Zebra white or black? It depends how close you are.... We are simply looking at cancer too close, not from a system-level broad perspective.
  • NickOttensNickOttens Barcelona, SpainPosts: 396 admin
    ymedan wrote:
    My gut tells me that the Mitochondria and Microbiota are talking...

    I see what you did there... :D

    @SamBlake, you may be interested in the discussion here.
  • marz62marz62 Posts: 48 ✭✭
    @ymedan - Ok, I'll bite (though I find 'systemic' solutions* sometimes hard to swallow). Intracellular communication typically involves signaling via small molecules (often peptides) and kinase cascades. Inter-cellular communication involves 'micro-vesicles' (lipid-based packets of genetic material [DNA, RNA] and peptides) which are endocytosed by the other cell. In both cases, peptides seem to be involved. Paint me a picture of how this peptidal trafficking would enable communication between organism and organelle, such that mitochondrial function is preserved/restored (= longevity).

    *a system can be as large or small as one chooses to define it -- never knowing for certain if the parameters so defined represent /describe the true and total system (where does the system begin and end?).
Sign In or Register to comment.