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Scientists map the genes behind diet and dementia risk

Concordance was high between imputed and sequenced APOE genotypes. Moreover, the researchers replicated known GWAS associations with diet-related biomarkers.

The authors also noted several limitations to provide context for future research. These include that the study population was predominantly of European ancestry, which may limit the generalizability of findings, and that the specific participant criteria (e.g., overweight, family history of dementia) mean the resource is not representative of the general population. They also advise that potential batch effects from specimen type and study site should be accounted for in future analyses.

This genetic resource enables analyses of genetic contributions to variability in cognitive responses to the MIND diet, supporting integrative analysis with other data types to delineate underlying biological mechanisms. The data will be made available to other researchers via The National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS).

Lysosomal membrane homeostasis and its importance in physiology and disease

Lysosomes degrade cellular components, and their membrane is an important signalling hub. Recent insights into the mechanisms that maintain lysosomal membrane homeostasis — including the interplay between membrane damage, repair, lysophagy and lysosome biogenesis — highlight their importance in physiology, in disease and during ageing.

Catalytic Research

NIA, NINDS: UNTANGLING THE VIRAL LINK TO NEURODEGENERATION

Scientists have long sought to understand the connection between viral infections and brain health. Can common viruses, which can reside unnoticed within our bodies, contribute to the development of neurodegenerative diseases such as Alzheimer’s and other forms of dementia? A study published in Science Advances led by researchers at the NIA tapped into data from thousands of human subjects offers compelling new insights into this enigmatic area of research.

The investigation examined the neurocognitive and plasma proteomic profiles of older adults in a community-based cohort from the Baltimore Longitudinal Study of Aging. Researchers focused on their antibody responses to four common coronaviruses and six herpesviruses with hopes of uncovering the molecular pathways linking the immune response to these viruses with brain aging and dementia risk.

Accelerating anti-aging cyclic peptide discovery through computational design and automated synthesis

Cyclic peptides, with their unique structures and versatile biological activities, hold great potential for combating skin aging issues such as wrinkles, laxity, and pigmentation. However, traditional discovery methods relying on iterative synthesis and screening are labor-intensive and resource-intensive. Here, we present an integrated platform combining automated rapid cyclopeptide synthesis, virtual screening, and biological activity assessment, enabling the transformation of designed cyclic peptide sequences into chemical entities within minutes with high crude purity. Using ADCP docking with the ADFR suite, we identified a series of novel cyclic peptides targeting JAK1, Keap1, and TGF-β proteins.

Cryonics & Cryptography | Ralph Merkle at Vitalist Bay

Veteran cryonicist and inventor of cryptographic hashing, Ralph Merkle, tells us how he came to decide that cryonics was a good idea. In his talk, Ralph discusses Information Theoretic Death, why information is so hard to destroy, and how advances in nano-tech might make cryonics revival possible.

Links:
• Cryosphere Discord server: https://discord.com/invite/ndshSfQwqz.
• Cryonics subreddit: https://www.reddit.com/r/cryonics/
#cryosphere

Is Altos Labs gearing up for clinical trials?

Longevity biotech giant Altos Labs has appointed Dr Joan Mannick as its Chief Medical Officer and head of product development, signaling a shift toward advancing clinical programs based on the company’s cellular rejuvenation technology. As Life Biosciences reportedly prepares to enter clinical trials with its partial epigenetic reprogramming candidate, is Altos about to join the party?

Altos, which launched with $3 billion in funding in 2022, is focused on reversing disease and age-related decline by restoring cellular health through partial epigenetic reprogramming, a technique inspired by the work of Nobel laureate Shinya Yamanaka and Juan Carlos Izpisua Belmonte. The company’s approach, which reverts cells toward a youthful state without altering their identity, has demonstrated benefits in animal models, extending both lifespan and healthspan in mice.

Although Altos has not yet launched human trials, the appointment of Mannick, who has significant experience designing and running clinical programs in aging biology, indicates the company is shifting into clinical applications of its technology. She will operate within Altos’ Institute of Medicine, collaborating with discovery and development teams to shape the clinical direction of its therapies.

Cardiac resident macrophages in cardiovascular disease: from physiology to pathology

Cardiovascular disease (CVD) is the leading cause of death and disease burden worldwide. Macrophages are important components of the internal immune cells, which profoundly affects the internal environmental homeostasis and repair after injury. Cardiac resident macrophages have been shown to regulate a variety of myocardial physiology and pathological activities. Homeostatic resident macrophages in the heart promote angiogenesis, remove ageing and dying cells and participate in cardiac electrical conduction. However, the role of cardiac resident macrophages is still not fully understood despite the growing attention they have received. This review provides an overview of macrophage biology and highlights prominent and emerging interrelationships and functions between cardiac resident macrophages and CVD, aiming to prove a description of the functional diversity of cardiac resident macrophages in different CVD to explore potential options to regulate them. This may provide opportunities for successful therapeutic interventions to improve the prognosis of patients with CVD.

Experiments add to evidence of links between amyloid deposits in brain and bone marrow

A recent study led by a team of researchers at The Johns Hopkins University School of Medicine examining aging mice has provided what is believed to be the first evidence that amyloid beta protein—small, sticky protein fragment found in people with Alzheimer’s disease (AD)—particles build up in the bone marrow of the animals, although not in the exact same form as the large, dense plaques found in the brains of people with Alzheimer’s disease.

“Although amyloid buildup has been found in organs outside the brain—such as the heart, kidneys, and nerves—it remains unclear whether similar deposits form in bone or with aging or in Alzheimer’s disease,” says contributing study author Mei Wan, Ph.D., professor of the department of Orthopedic Surgery.

“While brain amyloid has been extensively studied for its role in memory loss and neurodegeneration, far less is known about amyloid elsewhere in the body. In fact, almost nothing is known about whether amyloid forms in the skeleton or how it might contribute to age-related .”

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