NPC1 deficiency engages a lysosome - genome - immune program linked to neurodegeneration and cellular aging signatures

Lysosomal dysfunction is a prominent feature of neurodegeneration and aging, yet how primary defects in lysosomal trafficking are converted into progressive cellular decline remains poorly understood. Niemann Pick disease type C (NPC), caused by impaired …

39 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 17

Multimodal Deep Learning Reveals the Modular Genetic Architecture of Cardiovascular Aging

Age is the dominant risk factor for cardiovascular disease, yet individuals of the same chronological age can differ markedly in the organs and biological pathways through which cardiovascular vulnerability emerges. We used deep learning to …

39 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 17

Intermittent Fasting Attenuates Cognitive Decline in D-Galactose-Induced Aging Rats in Association with β-Hydroxybutyrate and PI3K/AKT/GSK-3β Signaling.

Age-related cognitive decline is a major public health concern, with few effective interventions available. Intermittent fasting (IF) has emerged as a promising metabolic intervention, potentially enhancing neuroprotection through increased β-hydroxybutyrate (BHB) production. This study aimed …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Replicative senescence of neural progenitors induces astrocyte senescence in 2D cultures and human midbrain organoids

Astrocyte senescence (astrosenescence) has emerged as a potential mechanism through which ageing may progressively impair glial homeostatic neuronal support and render the brain more vulnerable to neurodegenerative diseases such as Parkinsons disease (PD). Yet human …

34 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 12

Can senolytic drugs restore fertility in female mice with fatty liver disease?

Researchers treated female mice with fatty liver disease (MASLD) using senolytic drugs—compounds that eliminate senescent (aged) cells—and found pregnancy rates improved, particularly through reduced aging and inflammation in the ovaries. However, the treatment had limited …

39 Early
Design 6
Sample 6
Peer Review 13
Replication 5
Transparency 9

Ribonuclease DIS3 delays aging and senescence by generating tRNA halves.

Transfer RNA (tRNA) halves (tRHs) are generated via the cleavage of tRNAs, but their roles in aging and longevity remain poorly understood. Here, we demonstrate a direct role of tRHs in aging in metazoans. Through …

47 Early
Design 5
Sample 7
Peer Review 19
Replication 6
Transparency 10

Skin as a sentinel and modulator of systemic aging: a translational framework for evidence-based gerotherapeutics.

Aging is increasingly recognized as a dynamic and potentially modifiable biological process, yet translation of mechanistic discoveries into clinically validated interventions that extend human healthspan remains limited. Because dermatologists can directly observe, sample, and quantify …

44 Early
Design 5
Sample 7
Peer Review 16
Replication 6
Transparency 10

Eugenol from Syzygium aromaticum enhances longevity and proteostasis in aged yeast.

Clove (Syzygium aromaticum) extracts promote longevity in several model systems, yet the underlying molecular mechanisms responsible for the pro-longevity remain poorly defined. This study utilized a Saccharomyces cerevisiae model to investigate how clove extracts modulate …

44 Early
Design 5
Sample 7
Peer Review 16
Replication 6
Transparency 10

Decoupling AMPK from fatty acid synthesis allows maintenance of fitness late in life.

Although lifespan has long been the focus of ageing research, preventing functional decline late in life is a more pressing societal need. Here, we investigate the basis of senescence and declining fitness during replicative ageing …

44 Early
Design 5
Sample 7
Peer Review 16
Replication 6
Transparency 10

Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis

Idiopathic pulmonary fibrosis (IPF) is characterized by failed alveolar epithelial repair and progressive fibrotic remodeling. Although aberrant reprogramming of alveolar type 2 (AT2) cells and accumulation of transitional AT2 states are increasing recognized as central …

39 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 17

The longevity gene APOE2 enhances pericyte function and reduces lipid droplets.

Pericytes are critical for maintaining blood-brain barrier (BBB) integrity and have emerged as key contributors to Alzheimer's disease (AD) pathogenesis. Although the apolipoprotein E2 (APOE2) allele is associated with reduced AD risk and increased longevity, …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

How aging immune systems damage lungs—and what treatments might help

If your immune system ages slower, your lungs might stay healthier longer—but we need better treatments to prove it works.

This review examines how immunosenescence (age-related immune decline) drives lung diseases like COPD, fibrosis, and cancer, and surveys emerging treatments including senolytics, stem cell therapy, and lifestyle interventions. While it synthesizes current knowledge well, it's …

36 Early
Design 4
Sample 2
Peer Review 13
Replication 7
Transparency 10

Rejuvenation Potential of Developmental Genes Downregulated in Aging.

Partial reprogramming with Yamanaka factors effectively reverses cellular aging but poses potential oncogenic risks, limiting clinical translation. To identify safer rejuvenation induction factors (RIFs), we integrated five aging datasets and compared them with single-cell transcriptomics …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

Manganese overload as a previously underappreciated trigger of cellular senescence: unraveling mechanisms and therapeutic rescue by the senolytic quercetin.

Manganese (Mn) is an essential trace element, but excessive Mn exposure is associated with neurotoxicity and aging-related dysfunction. Whether Mn overload promotes cellular senescence and the mechanisms involved remain insufficiently defined. Here, we investigated Mn-induced …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Time-Restricted Feeding Prevents Cardiac Aging by Entraining Gut Microbiota Clock and Promoting Diurnal Rhythm Autophagy in Prediabetic Mice.

Time-restricted feeding (TRF) is a promising dietary strategy for delaying metabolic aging, yet its efficacy in cardioprotection across metabolic stages remains poorly understood. This study demonstrates that a 10-h TRF window significantly mitigates cardiac aging …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

How immune cells called NK cells shape healthy aging

This review synthesizes evidence that natural killer (NK) cells—a type of immune cell—undergo age-related changes that impair their ability to clear damaged cells and regulate inflammation, contributing to aging-related diseases. The authors propose NK cell …

35 Early
Design 4
Sample 2
Peer Review 11
Replication 9
Transparency 9

Can we reverse aging by partially reprogramming cells?

This review examines 'partial reprogramming'—a technique that temporarily activates rejuvenation factors to reverse aging hallmarks in cells and tissues without turning them into cancer-prone stem cells. Early evidence suggests it can restore tissue function and …

36 Early
Design 4
Sample 2
Peer Review 13
Replication 7
Transparency 10

An APOC1+ inflammatory CAF-like state drives a senescent, treatment-resistant niche in rheumatoid arthritis

Objectives: Rheumatoid arthritis (RA) synovitis frequently persists despite cytokine-targeted therapies, suggesting the existence of pathogenic stromal programs that sustain chronic inflammation independently of canonical immune pathways. Although synovial fibroblasts (SF) are increasingly implicated in treatment …

34 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 12

KDM4A-Driven Epigenetic Reprogramming as a Central Nexus Linking Metabolic Adaptation, Immune Remodeling, and Therapy Resistance in Cancer.

Cancer progression and treatment failure are driven not only by genetic alterations but also by the remarkable capacity of tumor cells to adapt to metabolic stress, immune surveillance, and therapeutic pressure. Epigenetic plasticity provides a …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Why Aging Cells Sometimes Help—and Sometimes Hurt—Muscle Repair

Understanding how aging cells block muscle repair could lead to new treatments to help older adults stay strong and independent.

This review examines cellular senescence (aging cells that stop dividing) in muscle regeneration, finding that senescent cells play a dual role: they can briefly help repair muscle after injury, but when they accumulate in aging …

37 Early
Design 4
Sample 2
Peer Review 15
Replication 7
Transparency 9