Aging is the lead risk factor for disease
BioViva’s work spans several genes and genetic strategies that play important roles in the biology of aging. Rather than looking for a single “longevity gene,” the company has investigated genes involved in different processes, including telomere maintenance, muscle preservation, mitochondrial function, metabolic regulation, genomic stability, and cellular reprogramming. The rationale is that aging is not caused by one biological failure. It involves multiple interconnected changes within cells and tissues, and different genes can influence different parts of that process.
One of BioViva’s longest-running targets is hTERT, the catalytic component of telomerase. Telomerase helps maintain telomeres, the protective structures at the ends of chromosomes. Telomeres generally shorten as cells divide, and critically short telomeres can contribute to cellular senescence and loss of replicative capacity. By working with hTERT, BioViva is investigating whether telomerase activity can be used to support cellular maintenance and extend the functional lifespan of cells.
BioViva has also investigated follistatin (FST), a protein that regulates several members of the TGF-beta superfamily. One of its best-known biological effects is its interaction with pathways involved in muscle growth and maintenance. Follistatin has therefore attracted considerable interest as a potential way of supporting muscle mass and function. BioViva has explored follistatin gene therapy as well as mRNA approaches, including work aimed at improving the duration and control of expression.
Another target is Klotho, a gene that has become particularly interesting in aging research because of its broad biological activity. Klotho is associated with regulation of phosphate metabolism and has been studied in connection with kidney function, cardiovascular biology, neurological function, and cellular stress responses. BioViva has investigated alpha-Klotho as a potential therapeutic target for age-associated conditions, including neurological and cardiovascular disease. The importance of Klotho to BioViva’s research reflects the company’s interest in genes whose effects extend across multiple tissues and biological systems.
BioViva has also worked with PGC-1α, a major regulator of mitochondrial biology. PGC-1α helps coordinate the expression of genes involved in mitochondrial biogenesis and energy metabolism. Mitochondria are responsible for much of the energy production within cells, and mitochondrial dysfunction is one of the recognized features of biological aging. By investigating PGC-1α, BioViva is targeting a pathway involved in maintaining cellular energy production and metabolic function.
SIRT6 represents another important part of BioViva’s work. SIRT6 is a member of the sirtuin family of proteins and is involved in chromatin regulation, DNA repair, genomic stability, and cellular metabolism. These functions are particularly relevant to aging biology because cells must continually repair DNA damage and maintain the integrity of their genome. SIRT6 therefore provides a way to investigate several fundamental processes involved in maintaining cellular function over time.
BioViva has also investigated FGF21, a hormone involved in metabolic regulation and energy homeostasis. FGF21 influences processes including lipid and glucose metabolism and has been extensively studied in the context of metabolic disease. Its biology makes it particularly relevant to conditions in which altered metabolism is an important component of disease. BioViva’s work with FGF21 expands its research beyond structural maintenance of cells and into the regulation of whole-body metabolic function.
Another area of BioViva’s work is partial cellular reprogramming using the OSK genes—OCT4, SOX2, and KLF4. These genes are three of the four Yamanaka factors originally identified for their ability to reprogram mature cells toward a pluripotent state. BioViva’s interest is not in completely converting mature cells into stem cells, but in the concept of partial reprogramming, in which reprogramming factors are expressed for a limited period with the goal of altering aspects of cellular age while retaining the cell’s differentiated identity. This approach is particularly significant because it addresses aging at the level of cellular state rather than targeting only one individual aging mechanism.
The OSK approach is fundamentally different from simply adding a longevity-associated gene. OCT4, SOX2, and KLF4are transcription factors that can alter the expression of large numbers of genes within a cell. In partial reprogramming, the objective is to use that regulatory capability to influence cellular characteristics associated with aging while avoiding complete dedifferentiation. Research in this area has examined changes in cellular function, epigenetic state, and tissue characteristics following transient exposure to reprogramming factors. BioViva is investigating this strategy as another potential avenue for addressing biological aging.
An important characteristic of these targets is that they operate through very different biological pathways. hTERT relates primarily to telomere maintenance and cellular replicative capacity; follistatin to tissue and muscle biology; Klotho to metabolic, renal, cardiovascular, and neurological processes; PGC-1α to mitochondrial function; SIRT6 to genomic maintenance and cellular regulation; FGF21 to metabolism and energy homeostasis; and OSK to cellular reprogramming and cellular identity. Together, they provide multiple avenues for investigating the biology associated with aging.
BioViva has also explored combinations of these targets rather than viewing each gene in isolation. The reasoning is that biological aging involves interconnected systems, and changing one pathway may not address changes occurring elsewhere in the cell. Combining targets that influence different aspects of cellular function provides a broader experimental framework for studying whether multiple aging-related mechanisms can be addressed simultaneously.
Importantly, these genes should not be described as established “longevity genes” that have been proven to extend human lifespan. Their significance comes from their biological functions and from the scientific research surrounding the pathways they regulate. BioViva’s work is focused on translating that underlying biology into therapeutic approaches, including gene therapy, mRNA-based strategies, and partial cellular reprogramming.
Taken together, hTERT, follistatin, Klotho, PGC-1α, SIRT6, FGF21, and the OSK reprogramming factors represent several different entry points into the biology of aging. They span telomere maintenance, tissue preservation, mitochondrial function, metabolic regulation, genomic stability, and cellular reprogramming. BioViva’s approach is therefore not simply to search for a single way to extend lifespan, but to investigate whether specific biological mechanisms that deteriorate with age can be targeted therapeutically and whether maintaining or restoring those mechanisms can help preserve human health and function.
