Live longer or age slower
Technological approach to old age
Blog of Philtech Initiative, Habr
Aging affects every person in the world – without exception. At the same time, modern science still has a rather weak idea of the mechanism of aging itself, and still cannot clearly answer even a simple question – what exactly does a person die from, from "old age" as such, or still from age-related diseases?
Traditional biology and genetics, giants of the pharmaceutical industry, technological visionaries-innovators and socially-oriented startups who are trying to improve the quality of life of the aging population approach the problem of aging from different sides. Some theories and approaches, as well as where to run with their solutions to aging-related social problems, will be discussed today.
"Traditional" scientific theories
Today, scientists have a number of theories that mainly study only certain aspects of aging, looking for some private mechanism that would explain it. Approaches to a comprehensive and systematic understanding of this process are still ahead.
Free radical theory of aging
The most popular theory a few decades ago says that aging occurs due to the accumulation of damage in cells caused by reactive oxygen species (ROS) - the so–called free radicals. This is a byproduct of normal cellular metabolism, but over time, ROS accumulate, begin to damage cells massively and provoke mutations.
Nowadays, this theory is refuted by a number of experimental observations on birds and small rodents – it turned out that the life expectancy of related species with the same level of ROS production differs by orders of magnitude. The naked digger (Heterocephalus glaber) distinguished itself the most – a small rodent of the digger family that lives abnormally long, on average up to 30 years (this is about ten times longer than all other rodents of this size known to science).
Terminal underreplication
This theory deals with telomeres – the end sections of chromosomes that shorten with each cell division. This is due to the fact that DNA polymerase (an enzyme involved in DNA replication) cannot synthesize a copy of DNA from the very end, but must add nucleotides to an already existing hydroxyl group. This phenomenon was first observed in the early 1960s by Leonard Hayflick, professor of microbiology and anatomy at the University of California, San Francisco, after whom the "Hayflick limit" was named - the maximum number of divisions that one cell can survive (for the human body, the limit was determined at 52 divisions).
But she didn't survive the test of time either. In the last two decades, biologists have observed the reverse process in the body of some seabirds, when telomeres, on the contrary, lengthen with age.
Epigenetic theories
Epigenetics is a fairly new branch of science that studies inherited changes in the function of genes. The term was first proposed in the middle of the XX century, but the modern definition of epigenetics was formulated almost today, in the 1990s, at the instigation of the American geneticist Arthur Riggs.
In the nucleus of each cell of the body, a genome is stored in a DNA molecule – an identical hereditary program that does not change throughout life and is not influenced by any external factors. How are cells formed from this identical code that are completely different in their structure, functions and processes occurring in them (from which, in turn, various tissues and organs grow)? Cells of different types activate different parts of the genome, and in the process of division they change the activity of individual genes. And this process is regulated by additional factors, a separate "control program", which is also recorded in the genome – this is the epigenome.
World science is just beginning to engage in serious systematic study of the epigenome – in 2007, the first publication was published within the framework of the American national Epigenome Programs, and three years later was founded The International Consortium of the Human Epigenome (IHEC), which brought together research projects in several countries.
Some aspects of epigenetic changes, such as DNA methylation or histone modifications, have already been studied in relative detail; many others have yet to be understood by biologists. But it is already clear that epigenetic processes most accurately correlate with age-related changes in the body, and most likely it is in them that the key to obtaining an accurate, complete and consistent theory of aging at the cellular level is hidden. There is every reason to believe that the complete mapping of the human epigenome will be as significant a breakthrough for modern science as the discovery of the cell by Robert Hooke in the XVII century and the complete decoding of human DNA in 2003.
Closed studies
Unlike scientific institutes and government-sponsored programs that disclose the results of all their research and experiments, many private R&D centers work on the problems of aging and age-related diseases behind closed doors. Sometimes secret laboratories of "big pharma" meet with the fuel and energy industry, and startups like California Calico, which was launched in 2013 with the support and funding of Google, appear.
The bio-pharmaceutical concern AbbVie is also investing in the company – in total, already $750 million (and plans to add another half a billion in the first quarter of 2019). Calico has not yet produced a single drug or biotech product, and so far only individual scientific articles published by its employees are publicly available.
Futurological theory
In opposition to other scientific theories is the original approach of the British gerontologist Aubrey de Grey, co-founder of the Methuselah Foundation, as well as the SENS Research Foundation, which spun off from him in 2009. Di Gray is convinced that there is no natural aging program in the human body at all, and all problems arise only because of the imperfection of the natural mechanisms of "anti-aging". He has developed a set of Engineering strategies for negligible aging (SENS) – therapeutic practices aimed at rejuvenation and regeneration of the body through neutralization of cancer mutations, cleaning of intracellular and intercellular debris, restoration of lost and destruction of malfunctioning cells.
To date, the entire SENS complex is a pure thought experiment, and there is no obvious progress towards practical implementation. And while some biologists and geneticists are skeptical about de Grey's research, he himself has managed to enlist the support of very authoritative figures, such as futurist Ray Kurzweil and Peter Thiel, donating millions of dollars to the development of the SENS Foundation.
Healthy longevity vs. long life
If the scientific community is more interested in aging as a biological mechanism, socially-oriented researchers and startups look at this problem from the point of view of the maximum long-term improvement in the quality of human life. The term "lifespan" in their lexicon is gradually being replaced by the concept of "healthy life span" (health span). In such a paradigm, the goal is to maximize the lengthening of the active and healthy phase of life, when all the interesting activities are available to a person, and to reduce the negative aspects of old age and old age. For example, the term "healthspan" appears in the description of a new track on biotechnology launched by YC Combinator earlier this year:
"I am pleased to present our new experiment on financing biomedical companies in the early stages of development - YC Bio.
Biology is a fairly extensive branch, and the first narrower topic that we want to focus on will be the extension of a healthy life and age–related diseases. We believe that now there is a great opportunity to help people keep their health much longer; perhaps this is one of the best ways out of the crisis in the health sector.
We have been financing biological companies for some time, and during this time we began to understand what works and what doesn't. We will try to develop a program based on this experience, and almost certainly something else will change in the process.
For YC Bio, we will launch a separate track, as was the case with YC AI, for example. But there are a few differences – instead of a standard deal for YC companies ($120,000 with a 7% stake), we will offer companies any amount from $500,000 to $1 million for a 10-20% stake, respectively. We will also help companies find a laboratory (through a partner), open access to a wide range of experts and other special offers.
We have prepared a separate application form in our RFS system for all biological companies that are engaged in aging and prolonging healthy life. But, of course, we are happy to invite all other bio-startups to apply for the standard YC program." – Sam Altman, January 2018.
Your project may be here
This fall, the Philtech accelerator launches a third stream - for startups that offer scalable technological solutions to the problem of aging. If you or your friends have ideas or a project for a technological solution to social, economic and cultural problems related to aging, it's time to apply: there is not much time left until September 20!
Portal "Eternal youth" http://vechnayamolodost.ru