Applying to Study Tissue Rejuvenation with an NIH STTR Grant through the National Institute on Aging (PA-27-102) with Project PALINGENESIS
Many years ago the SENS Research institute embarked on a bold mission to study the origin of diseases by considering aging as a pathology that could be studied and remedied. The program structured the causes of aging through the lens of tissue damage, the accumulation of molecules in tissue that cause stiffening and wrinkles (advanced glycation endproducts), and even through the lens of telomere destabilization and DNA damage.
Many years ago there was talk at the WEF that within years we would have nanomedicines that could cure diseases, we would be 3d printing organs that could be replaced, and we would even have the ability to cure infertility with artificial wombs. Many years has passed and so in my view, since science is a collaborative effort rather than one that should be expected to go through only monolithic institutions, and I have a goal to decentralize and open source scientific research, I've decided to try to pick up where this research has left off. It shouldn't be a requirement to rely on multinational corporations or institutions alone to progress our collective knowledge.
One example here is the mishandling of the covid pandemic. Studies showed a high success rate for point of access care especially when therapies were targeted like monoclonal antibodies. In fact, Nordic countries which had strong local infrastructure and universal point of access care without social distancing even outperformed countries which attempted a one-size-fits all strategy of social distancing and preventative measures to attempt to stop everybody from getting sick over the course of the pandemic. A better model would be to build the local and community infrastructure to handle problems as they arise and for when members of the public inevitably do get sick that a futile attempt at isolating every member of the public to prevent them from getting sick.
That does not mean a deregulation of sensitive research - I am currently scoping out potential university partners and experts for this project.
The plans are to start with the development of a novel measurement paradigm. Cellular senescence and remodeling of the dermal extracellular matrix are two of the best
characterized forms of age-related damage in human skin, yet no validated method measures them together in intact tissue without staining it. Skin aging is graded clinically with visual scales, and senescence is measured by staining biopsies, which destroys the tissue and cannot follow the same site over time. Label-free multiphoton microscopy can measure both kinds of damage from endogenous contrast. Second-harmonic generation (SHG) reports collagen content and organization, and autofluorescence of the metabolic cofactors NAD(P)H and FAD reports cellular metabolic state.
Both signals change with age, but they have mostly been studied one at a time, in small cohorts, with analysis methods that differ between laboratories. Dreamscape Systems Inc. proposes to combine them into a single Dermal Aging Index, produced by a standardized acquisition protocol and a
machine learning pipeline, and to test in Phase I whether the index tracks chronological age and molecular senescence burden in human skin. The study images 72 specimens of deidentified discarded surgical skin from donors aged 20 years and older, stratified by age and balanced by sex, on an established multiphoton and fluorescence lifetime imaging system at the research institution partner. Matched tissue from each specimen is stained for p16INK4a, p21, Lamin B1, and senescence-associated beta-galactosidase and scored by a blinded pathologist. Aim 1 establishes the reproducibility of each imaging feature. Aim 2 builds the index and tests its association with age under nested cross-validation. Aim 3 tests its association with senescence burden and, as an exploratory measure, its response to a senolytic in paired skin explants. A successful Phase I delivers a validated, pre-specified quantitative readout that Phase II will carry into living volunteers on a compact instrument, for use as an objective endpoint in dermatology, cosmetic, and senotherapeutic
studies.
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