Longevity has fascinated mankind for centuries, from ancient myths about fountains of youth to current speculation around caloric restriction.
With our increased scientific understanding of aging, clinical validation and commercialization of treatments are near. The goal is to extend lifespan as well as health span, and we may be looking at a future where the norm is to remain mentally and physically active at age 90, or even 100.
Healthy aging is influenced by a complex mixture of factors, including genetics, lifestyle, environment and nutrition. Teasing out and integrating these factors into a bigger picture is a major piece of the longevity puzzle. While still in the experimental stages, the world of biotech is connecting the pieces to find viable pathways, so let’s take a look at the players in the game.
The Long and Short of It
The connection between telomere length and aging gives us a glimpse into one of the many facets of longevity.
Telomeres are lengths of DNA, perched at the end of all chromosomes, made up of the repeating sequence of six nucleotides: TTAGGG. Our telomeres get shorter as we age, especially in cell types that lack an active telomerase enzyme, whose job is to ensure the entire telomere gets copied. A prevailing hypothesis is telomere length can predict life expectancy, with shorter telomeres corresponding to shorter lifespan.
Earlier this week, researchers at Stanford University (Palo Alto, CA) induced cells to transiently produce telomerase by delivering a modified telomerase-coding mRNA molecule to human muscle cells–resulting in a significant extension of the telomeres. This transient expression is a key advantage because unchecked telomere extension can cause cells to become cancerous. For now, the method is only used in the lab to increase the lifespan of cells, but it may have future clinical potential as an anti-aging treatment in humans.
Also undertaking the endeavor is Sierra Biosciences (Reno, NV), working to identify compounds capable of activating telomerase for clinical application.
REPAIRING OLD WITH NEW
A technique known as “parabiosis”–surgically joining two mice to share a circulatory system–demonstrated exposure to younger blood enabled older mice to repair damaged liver and muscle tissue, likely due to stem cell activation. Last year a Stanford research group, led by Tony Wyss-Coray, demonstrated old mice exposed to the blood of young mice have increased neuron growth. Wyss-Coray didn’t use parabiosis, rather he injected the plasma component of blood from younger mice into the older mice, replicating the same effect; good news for potential human patients.
The encouraging mouse studies prompted Wyss-Coray to start Alkhest (Menlo Park, CA). In September 2014, Alkhest started Phase I clinical trials, testing the infusion of plasma from young donors (under 30) into Alzheimer’s patients (over 50). The company’s quick move into human studies is thanks to plasma transfusions being a common and safe practice, allowing the IND requirement to be skipped. The full speed ahead approach allows the company to rapidly determine whether the technique is efficacious in people. Long term, isolating the exact protein(s) enabling the beneficial effect is a likely next move for Alkhest.
Simple to Complex
Longevity research spans the relatively low-tech idea of plasma transfusions to big data genomic sequencing, evidencing its complexity.
Human Longevity Institute (HLI; San Diego, CA), established in 2014 by Craig Venter, plans to tackle questions associated with longevity via human genome sequencing–with a near term goal of 40,000 entire genomes per year and long term 100,000 genomes per year. While many of the existing large-scale, full genome sequencing projects focus on cancer, HLI plans to sequence a diverse collection of genomes to tease out health and longevity patterns. Plans to mine the microbiomes and metabolomes of a sequenced group subset are also in the works.
Another longevity company backed by legendary players is California Life Sciences (Calico; South San Francisco, CA), founded in 2013 with financial backing from big data giant Google. Arthur Levinson, who made his name first as head of R&D and subsequently CEO and chairman of Genentech (South San Franciso, CA), is CEO of the startup. Apart from a stated mission “to harness advanced technologies to increase our understanding of the biology that controls lifespan”, Calico has been fairly secretive. Last fall’s announcement of a potential $1.5 billion, 10–year deal with AbbVie (North Chicago, IL) lifted the veil a little, suggesting a plan to move swiftly into the clinic on neurodegenerative diseases and cancer.
FROM Nontraditional to Traditional
Still others are approaching longevity from a more traditional drug discovery approach–analyzing pathways and identifying corresponding drug targets. One such target is a “jack of all trades” enzyme known as mTOR, which regulates the upward communication from amino acids, growth factor and insulin; it also monitors cell critical nutrients, energy levels, and oxygen.
Defects in mTOR signaling are linked to a wide range of age associated diseases including type 2 diabetes, Alzheimer’s and rheumatoid arthritis. A FierceBiotech 2014 “Fierce 15” company, Navitor Pharmaceuticals (Cambridge, MA) is on the mTOR bandwagon, with aims to develop proprietary technology to modulate mTOR in various disease states.