First Published in Masticadores [Taiwan] in June 2025

Native American flute tuned to Bageshri Raga
piano
kantele (digital)
synthesizers

The Little Organoid That Could

There's excitement in the air, as our stories of love and dementia both take a new twist.

The Marathon Years — 12. Taking the plunge

BUFFALO, NY — June 12, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 5, on May 3, 2025, titled “APOE genotype and biological age impact inter-omic associations related to bioenergetics.”

In this study, led by first author Dylan Ellis and corresponding author Noa Rappaport from the Institute for Systems Biology, researchers discovered that different versions of the APOE gene—particularly ε2 and ε4—are linked to metabolic patterns associated with aging and Alzheimer’s disease risk. Both variants were linked to increased levels of diacylglycerols, a type of fat molecule connected to insulin resistance and inflammation, suggesting shared disruptions in how the body regulates energy.

The research team analyzed data from over 2,200 adults without an Alzheimer’s diagnosis, exploring how APOE genotypes influence biological age, a measure of health that reflects how quickly or slowly someone is aging at a cellular level. They found that the same metabolic disturbances seen in ε2 carriers were also present in people considered biologically older, revealing unexpected overlap between genetic risk and aging-related metabolic changes.

To examine these connections in more detail, the researchers used a multi-omics approach, combining blood-based metabolism and protein data, gut bacteria analysis from stool samples, and clinical chemistry data. This method allowed them to map how genetic differences and biological aging affect the body’s energy systems. They observed altered connections between glucose metabolism, inflammatory markers, and key molecules that play roles in energy production, indicating early disruptions that could contribute to age-related diseases.

One of the study’s surprising findings was that the ε2 variant, usually associated with longer life and reduced Alzheimer’s risk, showed metabolic traits similar to those found in insulin-resistant individuals. This suggests that ε2 may carry metabolic disadvantages earlier in life, with its protective effects becoming more pronounced later. Conversely, ε4—linked to greater Alzheimer’s risk—may exert its influence based on interactions with lifestyle factors like diet, sex, and overall health status.

“‘Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying significantly increased associations between insulin resistance markers and energy-generating pathway metabolites.”

By identifying these shared biological signatures, this study offers a new framework for understanding how genes and metabolism work together to influence aging. These findings could support more personalized health strategies aimed at delaying biological aging and reducing the risk of chronic diseases. As aging populations grow worldwide, understanding these pathways is essential to improving healthspan.

DOI - https://doi.org/10.18632/aging.206243

Corresponding author - Noa Rappaport - noa.rappaport@isbscience.org

Video short - https://www.youtube.com/watch?v=75hZQoO5U0U

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Keywords - aging, apolipoprotein E (APOE), biological age, metabolism, Alzheimer’s disease (AD), insulin resistance

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Aging (Aging-US)

APOE Gene Variants Linked to Metabolic Signatures of Aging and Alzheimer's Risk

Original Lyrics and Music by: Nova J (I Still Remember Love)℗
Portuguese translation and arrangement by: Paulo Sergio Carvalho

Acordo num quarto que não conheço
As cortinas brilham, o sol é doce
Ela sorri e diz meu nome
Mas o dela... me foge, me consome

Ela me ajuda a me sentar
Traz meu prato, começa a cuidar
Tento comer, mas mal sinto o gosto
Ela segura minha mão, com tanto gosto

Ainda me lembro do amor
Mesmo quando o resto se apaga
Ainda me lembro do amor
E é disso que a vida se embala

Um homem entra e me chama “meu bem”
Seu rosto é calmo, sua voz vem
Não sei o lugar, nem o dia também
Mas com ele, me sinto bem

Me perco fácil lá no corredor
Esqueço o caminho, esqueço quem sou
Me encontram ali e me trazem de volta
Ninguém ri, ninguém me solta

Ainda me lembro do amor
Mesmo quando a mente falha
Ainda me lembro do amor
Como a luz do alpendre na madrugada

Tem uma canção dentro de mim
Cantarolo, mesmo sem o fim
Não sei de onde vem a melodia
Mas cantar me traz calmaria

Ainda me lembro do amor
Mesmo se eu perder meu lugar
Ainda me lembro do amor
Quando alguém vem me cuidar

Então se eu esquecer seu nome
Ou não souber onde estou
Por favor, não se esconda, nem some
Fica aqui comigo, por favor
Esqueço muita coisa, sim
Mas se tem algo que me guia, enfim…

Eu ainda me lembro do amor
Eu ainda me lembro do amor

Ainda me Lembro do Amor (Portuguese)

As a carer, you always have to be on the look-out for dementia dangers – even in the home.

The Marathon Years - 40. Through the Looking-Glass

Sometimes, I'm told, dementia can lead to inappropriate behaviour. But whose behaviour is inappropriate in this story — mine or Lena's?

TMY - 50. Inappropriate_Behaviour

This is a four-part choral composed in 2025 (Soprano, Alto. Tenor, Bass). The lyrics come from a poem, "Do Not ask Me to Remember", by Owen Darnell < https://www.alzheimers.net/do-not-ask-me-to-remember-poem>. The poem is about Alzheimers/dementia. The poem resonated with me because I watched my mother slowly lose herself to the void. Again, no singers, just woodwinds representing the four voices.

Do Not Ask Me to Remember

How is venture philanthropy revolutionizing Alzheimer's drug discovery? We sit down with Karen Harris, CFO at the Alzheimer's Drug Discovery Foundation, to explore their game-changing approach to funding early-stage research.

With $370M+ awarded to 765+ programs globally, the ADDF operates like a VC firm—using convertible debt and preferred equity to accelerate breakthrough treatments.
 
Topics:
Venture philanthropy vs traditional grants
Shift from amyloid to combination therapies
Blood-based biomarkers & precision medicine
NIH funding cuts impact on research ecosystem

Karen brings 20+ years investment banking experience to discuss how strategic capital is changing Alzheimer's research.

ADDF's Karen Harris: Investing in Alzheimer's Like a VC

FUCK NECK HURTS

DEMENTIA!!!!!!

On this episode of STILL HERE BITCH: Mature LGBTQ+ Dating & Relationships Podcast, Gerry chats with a gerontologist who specializes in SGM (Sexual and Gender Minority) - including LGBTQ+ - people. Dr. Meki Singleton and Gerry discuss why advanced care directives have become increasingly important, the many ways they can be set up, when you might start thinking about it, and who should be involved. Meki also offers advice to 20-year-olds on how to use the aging process to live a life with no regrets and mastering the art of caring for yourself. No matter what age you are, YOLO - so find out how to make it clap.

SHB EP 2.2: Advanced Care Directives - Ask a Woman Who Knows

Citeline places biopharma and medical device professionals, and those who focus on these industries, at the forefront of knowledge and insight, by providing the perfect combination of news and information together with penetrating insight and analysis. Citeline is a leader in the field of healthcare industry information.

STILL HERE BITCH: Mature LGBTQ+ Dating & Relationships is the first podcast about the unique relationship issues of LGBTQ+ people ages 40 and older. Watch on YouTube @stillherebitchpodcast.

2 european idiots making stupid music
anything said in the songs should NOT be taken seriously.

Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

I see music in the stars, I hear music when I sleep, its a never ending story... Paulo Sergio Carvalho, known to the music world as iPauloSergio, was born in the stunning city of Ponta Delgada in the Azores, Portugal. His early years were enriched by the lush landscapes and vibrant culture of the islands. At the tender age of 13, Paulo discovered his passion for music, immersing himself in the sounds of the piano, keyboards, and guitar. This early exposure laid the foundation for his lifelong love of music and set him on a path to become a multifaceted musician.

Paulo’s music is a rich tapestry woven from a wide array of influences. He admires legends such as Johnny Cash, Willie Nelson, and Bob Dylan for their storytelling prowess, while also drawing inspiration from the melodic genius of Billy Joel and the powerful anthems of Journey and Van Halen. Furthermore, the innovative sounds of electronic pop icons like Pet Shop Boys and Depeche Mode can be felt in his work. This fusion of genres reflects Paulo's ability to connect with a diverse audience and create music that resonates on multiple levels.

In addition to his solo pursuits, Paulo has collaborated with fellow musician iGracie to write songs for various bands, including the country outfit Devils and Debutantes and the indie rock group Love Bomb Poets Society. These partnerships have allowed him to explore different musical styles and expand his songwriting repertoire, blending heartfelt lyrics with catchy melodies that appeal to listeners across genres.

Bitcoin address for tips: bc1ql38nsruy9s3ejfzwpcvuyuw7qczapcevdknmjn

I'm using SoundCloud to release audio versions of the latest chapters from my book 'The Marathon Years' - the story of our decade-long battle defying dementia. (Oh, and It's a love story too) Catch new episodes at my website Miles Posts, where you can also sign up for my weekly newsletter keeping you updated with all the latest news and releases..

New tracks tagged #alzheimers