Can you slow the aging process? Study reveals which interventions might help

Good news! Again, lifestyle improvements (healthier diet, less stress, more physical exercise and so on) are confirmed to be very strong when it comes to healthy aging and long life. The way one ages is to a large extent a personal choice.

Notice this study is focused on epigenetic aging, which may or may not be a narrow focus of the complex process of aging.

"... Using a new class of DNA-based blood tests, they found that lifestyle interventions and certain drug treatments indeed appear to slow the aging process, while over-the-counter supplements don’t have much effect. ...

For their analysis, the researchers primarily used a type of blood-based biomarker known as epigenetic clocks, which estimate epigenetic or biological age by measuring the pattern of methyl groups (basic chemical structures that act like tags) attached to a person’s DNA.

As people age, these chemical tags change, previous research has shown. Successful anti-aging interventions can reverse the tags. Computer algorithms are then able to use the changes observed in these tags to estimate a person’s epigenetic “age.” ...

The researchers tested four categories of intervention: pharmacological drugs, lifestyle-based changes, over-the-counter supplements, and medical procedures. They found that lifestyle interventions, such as a combination of a healthy diet (whether it’s Mediterranean, low-carb, or low-fat) and exercise, consistently decreased epigenetic age.

Pharmacologic interventions — including metformin and semaglutide, prescription medications used for metabolic control and weight management, and anti-TNF therapies, which use biologic medications to target an immune system protein that triggers harmful inflammation — decreased epigenetic age the most. (TNF, or tumor necrosis factor, is an immune-system protein that helps fight inflammation-related injury.) ..."

From the abstract:

"Aging biomarkers can potentially allow researchers to rapidly monitor the impact of an aging intervention without the need for decade-spanning trials.

However, before the use of aging biomarkers, such as epigenetic clocks, as surrogate endpoints, their responsiveness to interventions that target aging must be tested.

Here we curate TranslAGE, a harmonized database of 51 public and private longitudinal interventional studies, and calculate a consistent set of 16 prominent epigenetic clocks for each study, along with 94 other DNA methylation (DNAm) biomarkers that can help explain the changes observed for each clock.

Using this database, we discover patterns of responsiveness across a variety of interventions and DNAm biomarkers.

For example, clocks trained to predict mortality or pace of aging show the strongest responses across all interventions and show consistent results with one another; 

pharmacological and lifestyle interventions drive the strongest responses from DNAm biomarkers; and the characteristics of the study population and study duration are key factors in determining the responsiveness of DNAm biomarkers to an intervention.

Moreover, clocks with multiple subscores (that is ‘explainable clocks’) provide specificity and greater mechanistic insight into the responsiveness of interventions than single-score clocks.

These findings can help to design future clinical trials by guiding the choice of interventions and of specific subsets of DNAm biomarkers to minimize multiple testing, study duration, study population and sample size, with the eventual aim of uncovering DNAm biomarkers that can be used as surrogate aging endpoints."

Can you slow the aging process? Study reveals which interventions might help | Yale News "A new Yale analysis found that diet, exercise, and some medications can slow the aging process, while over-the-counter supplements appear to have little effect."

Responsiveness of epigenetic aging biomarkers to longevity interventions in humans (open access)

Fig. 1: Current paradigms to study the responsiveness of DNAm biomarkers and their limitations.

Fig. 3: Interventions and their effects on 16 prominent DNAm biomarkers.

Researchers uncover shared molecular mechanisms across three types of dementia

Good news!

"Researchers have for the first time identified degeneration-associated “molecular markers” – observable changes in cells and their gene-regulating networks – that are shared by several forms of dementia that affect different regions of the brain. Critically, the UCLA-led research ... also identified markers specific to different forms of dementia. The combined findings represent a potential paradigm shift in the search for causes, treatments and cures. ...

They performed single-cell genomic analysis on more than 1 million cells to identify distinct and shared molecular markers in three related conditions: Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy. In addition to validating changes previously observed in Alzheimer’s, they identify dozens of cell types whose changes are shared across multiple dementias and several cell types whose changes in disease were specific to a single disorder, many of which had not been previously identified. ...

The researchers:

• Identified unique changes specific to Alzheimer’s disease and demonstrated that several findings in Alzheimer’s were also observed across the other disorders, identifying targets for therapeutic development.
• Found that “cellular resilience programs” – molecular mechanisms that support cells in response to injury – activated or failed differently, when comparing the same cell types across disorders.
• Were surprised to discover that each of the three disorders had changes in cells of the primary visual cortex – the area of the brain that processes visual information and which was thought to be unaffected by dementia. In progressive supranuclear palsy, this discovery revealed previously unknown changes in brain cells called astrocytes.
• Identified specific changes in the expression of certain tau-related genes and others in progressive supranuclear palsy. These appear to correlate with the unique pattern of brain cell degeneration that is observed in progressive supranuclear palsy.

..."

From the highlights and abstract:

"Highlights

• Perform comparative genomic analysis of AD, bvFTD, and PSP at the single-cell level

• Pinpoint markers and candidate drivers of selective neuronal vulnerability in dementia

• Identify disorder-specific microglia, astrocyte, and oligodendrocyte glial-immune states

• Causal genetic risk impacts disorder-specific gene regulatory networks and cells

Summary

The development of successful therapeutics for dementias requires an understanding of their shared and distinct molecular features in the human brain. We performed single-nuclear RNA-seq and ATAC-seq in Alzheimer’s disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), analyzing 41 participants and ∼1 million cells (RNA + ATAC) from three brain regions varying in vulnerability and pathological burden. We identify 32 shared, disease-associated cell types and 14 that are disease specific. Disease-specific cell states represent glial-immune mechanisms and selective neuronal vulnerability impacting layer 5 intratelencephalic neurons in AD, layer 2/3 intratelencephalic neurons in FTD, and layer 5/6 near-projection neurons in PSP. We identify disease-associated gene regulatory networks and cells impacted by causal genetic risk, which differ by disorder. These data illustrate the heterogeneous spectrum of glial and neuronal compositional and gene expression alterations in different dementias and identify therapeutic targets by revealing shared and disease-specific cell states."

Researchers uncover shared molecular mechanisms across three types of dementia | UCLA "The discovery of genes that marked vulnerable neurons could open options for therapeutic approaches"

Cross-disorder and disease-specific pathways in dementia revealed by single-cell genomics (no public access)

Graphical abstract

Detecting Alzheimer's 20 years before onset using various biomarkers

Good news!

Clues from DNA could help predict growth of prostate cancer

Cancer is history! This seems to be very promising research with implications for other cancers as well!

"Researchers ... have identified 1,178 biomarkers in men’s genomes ... that predict how an individual person’s prostate cancer will grow. ... The researchers focused ... on ... DNA methylation. ... Some of these parts control cellular functions, such as the production of proteins. When tumors form, they have the ability to hijack DNA methylation to help the cancer cells grow and spread by turning cellular functions on and off. ... In the new study, researchers discovered that variations in the DNA a person is born with make it easier or harder for a tumor to use methylation to turn off and on cancer genes."

Clues from DNA could help predict growth of prostate cancer | UCLA: The finding suggests that predicting how a person’s cancer will evolve may lie in their inherited genetic material.