Longaevus Technologies

Longaevus Technologies is a longevity biotech parent company with several incubated and spin-out companies operating under a venture creation model. They say they “aim to revolutionise anti-ageing therapeutics and extend the human lifespan by two decades.” It is led by Ivan Morgunov (cofounder and CEO) and Anna Vakhrusheva (cofounder, CTO, and CEO of incubated company Remodel). Additionally, Alexey Moskalev is a cofounder and serves as a scientific director and Chief Scientist of portfolio company Elastin Biosciences.

While rejecting the Hallmarks of Aging, the company posits the existence of “longevity bottleneck” processes that serve a similar role, being metabolic processes that limit human lifespan and contribute to specific diseases of aging. Among these, they list reactivation of retrotransposons, increased extracellular matrix stiffness, declining telomerase activity, “reversal of mitochondrial dysfunction,” “Restoration of autophagy regulation,” “and more.”

Longaevus states that it screens for new candidates using its Targetome in silico platform and Excelsius ex vivo platform.

Elastin Biosciences
Elastin Biosciences (EB) is a self-described “emerging” longevity biotech company focused on developing small-molecule therapies to address diseases driven by the loss of and defects in elastin. It is a spinoff company of Longaevus Technologies but is still listed in its portfolio.

As the name suggests, elastin is a key protein that gives tissues elasticity. Mechanical stress, protein-degrading enzymes, and free radicals progressively degrade our elastin structures with age, and they are not replaced due to the deactivation of elastin synthesis under physiological conditions during early development. Damaged elastin contributes to age-related stiffening of the arteries (and thus hypertension, kidney disease, aneurysm, and stroke), the lungs (and hence age-related loss of lung capacity, emphysema, and perhaps idiopathic pulmonary fibrosis), amongst other tissues.

In September 2023, EB announced that they had “identified three novel drug combinations that inhibit elastin degradation and foster its deposition, leading to an increase in elastin expression by 5-fold, and improving aortic elasticity in aged mice in-vivo.”. CEO Idriss said in an interview “that the quality of the elastin fibers is actually very good as well,” and that they had observed no side effects in the mice other than itching at the injection site. These findings were confirmed and expanded in later studies.

EB highlighted their candidates’ potential to treat conditions such as abdominal aortic aneurysm and Williams syndrome, a congenital disease that results in haploinsufficient expression of roughly 27 gene, including ELN, the gene that codes for elastin. This leads to abnormalities in connective tissue, including supravalvular aortic stenosis.

Remodel
Remodel is working to develop glucosepane crosslink breakers and “protein engineering approaches to remodel the aged [extracellular] matrix.”

Researchers have for some time thought that glucosepane is the most common Advanced Glycation End-product (AGE) crosslink in aging collagen. The long-lived collagen proteins that give structure to our arteries, skin, and other tissues are constantly exposed to blood sugar and other reactive molecules in the bloodstream. These sugar molecules can sometimes bind to collagen and form initially-reversible adducts that — if not reversed — can mature into AGE that alter the physical properties of tissues and cause inflammation. AGE crosslinks, in particular, bind adjacent collagen strands together and so limit their motion, and are therefore thought to contribute to the gradual stiffening of tissues, particularly blood vessels.

This crosslinking is thought to contribute to increasing arterial stiffness and systolic blood pressure, resulting in kidney damage, heart failure, and an increased risk of stroke. Cleaving these crosslinks would allow adjacent collagen strands to move independently again, potentially restoring arterial flexibility and preventing these disabling outcomes.

Remodel
Remodel is working to develop glucosepane crosslink breakers and “protein engineering approaches to remodel the aged [extracellular] matrix.”

Researchers have for some time thought that glucosepane is the most common Advanced Glycation End-product (AGE) crosslink in aging collagen. The long-lived collagen proteins that give structure to our arteries, skin, and other tissues are constantly exposed to blood sugar and other reactive molecules in the bloodstream. These sugar molecules can sometimes bind to collagen and form initially-reversible adducts that — if not reversed — can mature into AGE that alter the physical properties of tissues and cause inflammation. AGE crosslinks, in particular, bind adjacent collagen strands together and so limit their motion, and are therefore thought to contribute to the gradual stiffening of tissues, particularly blood vessels.

This crosslinking is thought to contribute to increasing arterial stiffness and systolic blood pressure, resulting in kidney damage, heart failure, and an increased risk of stroke. Cleaving these crosslinks would allow adjacent collagen strands to move independently again, potentially restoring arterial flexibility and preventing these disabling outcomes.

SeneXcell
Although the name suggests that the company develops senotherapeutics, SeneXcell emphasizes that the chronic inflammation of aging is driven by multiple mechanisms, including DNA damage and immunosenescence in addition to senescent cells. Instead of focusing on the proximate factors in the inflammatory cascade, SeneXcell seeks to identify genes that become overactivated during aging and pathological inflammatory processes, arguing that they can thereby restore homeostasis to the entire inflammatory cascade.

Using primary skin fibroblasts from elderly persons, SeneXcell screened for genetic targets using lentiviral shRNA, using inflammatory markers and “multiple markers to assess various changes and cell viability readouts.” This led to the identification of two target genes, codenamed LONG-001 and LONG-002, whose inhibition led to “a remarkable rejuvenating effect” on these cells.

SeneXcell says they are “committed to presenting potential leads for this target in the upcoming year” (the date of writing is unclear), and indicate that their initial indications will be psoriasis and rheumatoid arthritis.

Combobioscience
The company’s website says, “Ageing is a multifaceted process that impacts various pathways, and we are confident that achieving success in extending lifespan requires the synergy of multiple components. The project aims to develop synergistic combinations of small molecules that can impact multiple ageing pathways and induce epigenetic reprogramming. The first combination aimed to tackle neurological ageing.” No additional information is available.