Ironically, the first person to be diagnosed with what is now Alzheimer’s disease was missing its major risk factor. When she first began showing symptoms of dementia in 1901, Auguste Deter was not particularly old. Despite Deter’s case, aging is the largest risk factor for developing Alzheimer’s, by a large margin. But “geroscience has not been translated into drugs for Alzheimer’s disease,” Howard Fillit, Alzheimer’s Drug Discovery Foundation co-founder and chief scientific officer, told BioWorld. “We’re just starting to see that cross-fertilization now.” This first article of a three-part BioWorld series on Alzheimer’s disease looks at how a group of researchers, as well as some startups, are trying to approach Alzheimer’s via an aging lens.

Alzheimer’s disease (AD) is recognized worldwide for its debilitating symptoms of declining cognitive function and gradual memory loss. What remains less clear is exactly what causes the neurodegenerative disease, and how to treat it. “Alzheimer’s disease is characterized by two key pathologies – beta-amyloid plaques and tau neurofibrillary tangles.” Seung-Yong Yoon, CEO of Adel Inc., told BioWorld. “Adel is looking to develop a tau-targeting drug, considering tau has been more correlated with AD symptom progression, and the industry’s need for tau pipelines.”

Deep learning algorithms have enabled the discovery of molecular structures of interest in biomedicine to design treatments against aggressive diseases such as idiopathic pulmonary fibrosis (IPF). Scientists at Insilico Medicine Inc. selected a target for IPF using artificial intelligence (AI), then designed an inhibitor to block it, and tested it in vitro, in vivo, and in clinical trials.

The third day of the AD/PD 2024 conference in Lisbon started with a plenary lecture given by Professor Howard Fillit entitled, “Translating the biology of aging into new therapeutics for Alzheimer’s disease.” Fillit, a recognized neuroscientist and geriatrician, and co-founder of the Alzheimer’s Drug Discovery Foundation (ADDF), pointed to the geroscience hypothesis which postulates that targeting aging processes may result in preventive and therapeutic options for diseases of old age, including Alzheimer’s disease (AD).

“Aging is not only slow, but it is irreversible, and that is what most people have been suspecting,” Gero Pte Ltd.’s CEO Peter Fedichev recently told BioWorld. “[But] aging is not an inevitable part of human existence.” By setting limits to what science can do – and not do – for aging, the Palo Alto, Calif.- and Singapore-based generative artificial intelligence (AI) biotech Gero is trying to figure out and, at the same time help the industry, “see what is actionable, reversible and what may not be” to help people avoid “hitting their heads against the wall” when tackling aging and aging-related diseases.

Scientists have discovered that a small chemokine protein released by activated platelets, platelet factor 4 (PF 4), reduced neuroinflammation, and improved cognition in aged mice. The study was published on Aug. 16 in the online edition of Nature.

Integrated Biosciences Inc., an early-stage startup that is combining synthetic biology and machine learning in the hunt for drugs that tackle cell senescence, has demonstrated its capabilities in a newly published study in Nature Aging on May 4, 2023, which employed artificial intelligence to identify three novel compounds that are highly selective for Bcl-2 and that exhibit favorable medicinal chemistry profiles.

Compared to the issues that come with, say, a failing liver, skin aging can look like more of a vanity problem. But aging in both tissues, and multiple others, is driven by the same underlying molecular mechanisms. One of those mechanisms is fibrosis, the cross-linking of extracellular matrix (ECM) proteins that leads to tissue stiffening. Anti-aging company Cambrian Biopharma Inc. has argued that stiffening of the ECM should be considered one of the formal hallmarks of aging.

The first in vivo cell atlas of senescent tissue in skeletal muscle has identified the damaging properties of these cells and explained why they block muscle regeneration. According to a study at Pompeu Fabra University led by scientists from Altos Labs Inc., cell damage caused the senescence of the cells, which secreted toxic substances into the surrounding microenvironment, causing fibrosis and preventing tissue regeneration.

By independently manipulating the lifespan of worms and one of its purported biomarkers, namely, the cessation of vigorous movement (CVM), investigators at the Center for Genomic Regulation (CRG) in Barcelona have demonstrated that the two are driven by partly independent processes.