Anti-Aging Startup Raises $116 Million With big VCs and Amazon CEO Jeff Bezos Backing

Unity Biotechnology said Thursday that it attracted support for the Series B funding round from traditional biotech investors including Fidelity Management and Research Co., Arch Venture Partners, Partner Funds Management and Venrock. The San Francisco-based startup is also backed by Bezos Expeditions, the investment arm of Inc. Chief Executive Officer Jeff Bezos.

The companies goal is 25 years (2041) from now, people coming of age grow up in a world where it’s considered relatively normal to have an extended average lifespan, and more profoundly, it’s an era where osteoarthritis and age-related eye diseases are only things you read about in books.

“We don’t expect people to be living to 150 years, even in the wildest version of success,” he said. “But we do expect people to live free of a variety of chronic diseases.”

While ambitious, David says the biotech startup is grounded in serious science. Unity focuses on so-called senescent cells in the body that have stopped dividing. Studies have shown that senescent cells are associated with chronic inflammation and accumulate in the same areas where age-related diseases appear, such as aching joints, degenerating eyes and diseased hearts, David said.

Unity plans to start human trials in the next 12 to 18 months, beginning with eye diseases, including glaucoma and age-related macular degeneration, and osteoarthritis, according to Leonard. The company’s drug will be injected locally into the eye or joint to wipe out the senescent cells.

David and Chief Executive Officer Keith Leonard previously co-founded Kythera Biopharmaceuticals Inc., a maker of treatments for double chins and male pattern baldness. They sold the company to Allergan Plc for $2.1 billion in June 2015. David is also a partner at Arch Venture Partners, which invested in this round.

Unity is part of a wave of new companies chasing after the fountain of youth. Calico, a subsidiary of Google parent Alphabet Inc. founded in 2013, has partnered with biotechnology firm AbbVie Inc., though it has been secretive about what it’s working on. Elysium Health is another startup that’s already selling a dietary supplement that it claims will help with metabolic processes such as cellular detoxification and DNA repair.

Unity is the 10th biotechnology startup to complete a fundraising round for $100 million or more in 2016, according to research company PitchBook Data Inc. The largest deal was Moderna Therapeutics’ $474 million Series F round in September, according to PitchBook.

Two Unity co-founders published a study shows that senescent cells are key drivers of plaque formation in atherosclerosis, a disease in which plaque buildup narrows the arteries, potentially causing heart attacks or strokes. Clearing those cells in mice fed a high-fat diet reduced the plaque and also made it less likely to break into pieces that can block blood vessels.

Strategies for Engineered Negligible Senescence (SENS)

The prominent antiaging research group SENS is led by Aubrey de Grey. They have identified seven forms of age related damage. Senescent cells are one of those types of damage.

Seven main categories of ‘damage’, seven alterations whose reversal would constitute negligible senescence:

cell loss or atrophy (without replacement),
oncogenic nuclear mutations and epimutations
cell senescence (Death-resistant cells)
mitochondrial mutations,
Intracellular junk or junk inside cells (lysosomal aggregates),
extracellular junk or junk outside cells (extracellular aggregates),
random extracellular cross-linking

Types of aging damage and treatment schemes
Nuclear mutations/epimutations—OncoSENS
These are changes to the nuclear DNA (nDNA), or to proteins which bind to the nDNA. Certain mutations can lead to cancer.

This would need to be corrected in order to prevent or cure cancer. SENS focuses on a strategy called “whole-body interdiction of lengthening telomeres” (WILT), which would be made possible by periodic regenerative medicine treatments.

Mitochondrial mutations—MitoSENS
Mitochondria are components in our cells that are important for energy production. Because of the highly oxidative environment in mitochondria and their lack of the sophisticated repair systems, mitochondrial mutations are believed to be a major cause of progressive cellular degeneration.

This would be corrected by allotopic expression—copying the DNA for mitochondria completely within the cellular nucleus, where it is better protected. De Grey argues that experimental evidence demonstrates that the operation is feasible, however, a 2003 study showed that some mitochondrial proteins are too hydrophobic to survive the transport from the cytoplasm to the mitochondria.

Intracellular junk—LysoSENS
Our cells are constantly breaking down proteins and other molecules that are no longer useful or which can be harmful. Those molecules which can’t be digested accumulate as junk inside our cells, which is detected in the form of lipofuscin granules. Atherosclerosis, macular degeneration, liver spots on the skin and all kinds of neurodegenerative diseases (such as Alzheimer’s disease) are associated with this problem.

Junk inside cells might be removed by adding new enzymes to the cell’s natural digestion organ, the lysosome. These enzymes would be taken from bacteria, molds and other organisms that are known to completely digest animal bodies.

Extracellular junk—AmyloSENS
Harmful junk protein can accumulate outside of our cells. Junk here means useless things accumulated by a body, but which cannot be digested or removed by its processes, such as the amyloid plaques characteristic of Alzheimer’s disease and other amyloidoses.

Junk outside cells might be removed by enhanced phagocytosis (the normal process used by the immune system), and small drugs able to break chemical beta-bonds. The large junk in this class can be removed surgically.

Cell loss and atrophy—RepleniSENS
Some of the cells in our bodies cannot be replaced, or can be only replaced very slowly—more slowly than they die. This decrease in cell number affects some of the most important tissues of the body. Muscle cells are lost in skeletal muscles and the heart, causing them to become frailer with age. Loss of neurons in the substantia nigra causes Parkinson’s disease, while loss of immune cells impairs the immune system.

This can be partly corrected by therapies involving exercise and growth factors, but stem cell therapy, regenerative medicine and tissue engineering are almost certainly required for any more than just partial replacement of lost cells.

Cell senescence—ApoptoSENS
Senescence is a phenomenon where the cells are no longer able to divide, but also do not die and let others divide. They may also do other harmful things, like secreting proteins. Degeneration of joints, immune senescence, accumulation of visceral fat and type 2 diabetes are caused by this. Cells sometimes enter a state of resistance to signals sent, as part of a process called apoptosis, to instruct cells to destroy themselves.

Cells in this state could be eliminated by forcing them to apoptose (via suicide genes, vaccines, or recently discovered senolytic agents), and healthy cells would multiply to replace them.

Extracellular crosslinks—GlycoSENS
Cells are held together by special linking proteins. When too many cross-links form between cells in a tissue, the tissue can lose its elasticity and cause problems including arteriosclerosis, presbyopia and weakened skin texture. These are chemical bonds between structures that are part of the body, but not within a cell. In senescent people many of these become brittle and weak.

SENS proposes to further develop small-molecular drugs and enzymes to break links caused by sugar-bonding, known as advanced glycation endproducts, and other common forms of chemical linking.

Science – Senescent intimal foam cells are deleterious at all stages of atherosclerosis

Wreaking havoc while (growth-)arrested

Cells enter a state of senescence in response to certain stresses. Studying mouse models, Childs et al. examined the role of senescent lipid-loaded macrophages (so-called “foam cells”) in the pathogenesis of atherosclerosis. At early stages of atherosclerosis, senescent foam cells promoted the expression of inflammatory cytokines. At later stages, they promoted the expression of matrix metalloproteases implicated in the rupture of atherosclerotic plaque, which can lead to blood clots. Experimental removal of the senescent cells had beneficial effects at both stages of the disease.


Advanced atherosclerotic lesions contain senescent cells, but the role of these cells in atherogenesis remains unclear. Using transgenic and pharmacological approaches to eliminate senescent cells in atherosclerosis-prone low-density lipoprotein receptor–deficient (Ldlr–/–) mice, we show that these cells are detrimental throughout disease pathogenesis. We find that foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis, where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. Together, these results demonstrate that senescent cells are key drivers of atheroma formation and maturation and suggest that selective clearance of these cells by senolytic agents holds promise for the treatment of atherosclerosis.

Nature – Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16Ink4a (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16Ink4a-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16Ink4a-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16Ink4a-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.

SOURCES- Science, Nature, Unity Biotechnology, Bloomberg News