Cellular senescence is an irreversible cell cycle arrest, triggered by stressors like telomere shortening, DNA damage, and oncogenic signaling.
Category: life extension
Polyamine metabolism as a regulator of cellular and organismal aging
Polyamines — putrescine, spermidine, and spermine — are ubiquitous cationic molecules that are essential for cellular proliferation and homeostasis. Their intracellular concentrations decline with age, contributing to physiological and cognitive deterioration. Recent studies have revealed that spermidine supplementation extends lifespan and improves cognitive and cardiac function in various model organisms, suggesting that maintaining polyamine balance has anti-aging potential. Polyamine metabolism is tightly regulated through biosynthesis, degradation, and transport; however, age-associated upregulation of spermine oxidase (SMOX) and accumulation of its toxic byproduct acrolein promote oxidative damage and cellular senescence. Suppressing SMOX activity or polyamine degradation attenuates senescence markers and DNA damage, highlighting spermine catabolism as a therapeutic target. Polyamines also modulate epigenetic regulation, including DNA methylation and histone acetylation, thereby influencing gene expression and chromatin structure during aging. Moreover, polyamine-dependent hypusination of eIF5A sustains protein synthesis in senescent cells. These multifaceted actions indicate that polyamine metabolism integrates redox control, translational regulation, epigenetic maintenance and autophagy to determine cellular and organismal longevity. While animal studies demonstrate clear anti-aging effects of spermidine and spermine, human clinical evidence remains limited, with variable outcomes likely due to bioavailability and metabolic conversion. Future strategies combining dietary or probiotic polyamine enhancement, enzyme-targeted inhibitors, and personalized metabolic interventions hold promise for extending healthspan. Collectively, maintaining optimal polyamine homeostasis emerges as a key approach to counteract aging and age-related diseases.
Anti-aging effect of Hedgehog signaling
Aging weakens the body’s ability to maintain balance and repair damage, increasing vulnerability to disease. This study reveals that the Hedgehog (Hh) signaling pathway plays a crucial role in preserving tissue integrity and regenerative capacity. Using animal models, researchers found that activating Hh signaling in multiple tissues such as the liver and brain enhances tissue repair and mitigates age-related functional decline. These findings suggest that targeting Hh signaling could be a promising strategy to promote healthy aging by enhancing regeneration and alleviating age-related dysfunction.
This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
Convergence of aging- and rejuvenation-related epigenetic alterations on PRC2 targets
Rejuvenation of tissues in physiologically aging mice can be accomplished by long-term partial reprogramming via expression of reprogramming factors (Oct4, Sox2, Klf4, and c-Myc). To investigate the epigenetic determinants of partial reprogramming-mediated rejuvenation, we used whole-genome bisulfite sequencing to carry out unbiased comprehensive profiling of DNA methylation changes in skin from mice subjected to partial reprogramming, as well as young and untreated old controls. We found a striking convergence of age- and rejuvenation-related epigenetic alterations on targets of the Polycomb repressive complex 2 (PRC2), with increased DNA methylation level and entropy over these regions. Native ChIP demonstrated extensive loss of H3K27me3 in aged epidermis compared to young, partially overlapping regions with age- and rejuvenation-related DNA methylation changes. In addition, large H3K9me2-marked “LOCK” heterochromatin domains defined the boundaries for hypomethylated highly entropic regions during aging. These results are also supported by a likewise prominent enrichment of PRC2 targets in gene expression data, suggesting that PRC2 activity can modulate aging and mediate tissue rejuvenation.
Japanese government panel endorses Sumitomo Pharma’s iPS-derived treatment for Parkinson’s
The expert council of the Japanese Ministry of Health has approved two regenerative medicine drugs based on induced pluripotent stem cells (iPSCs) — a cure for Parkinson’s disease and heart failure. If the health minister approves the experts’ decision, Japan will become the first country in the world to allow the commercial sale of such products — almost 20 years after the discovery of the technology itself.
Japan’s health ministry said on Thursday a panel of specialists had endorsed Sumitomo Pharma’s iPS cell-derived treatment for Parkinson’s disease, paving the way for the world’s first medical products based on the technology.
A gel for wounds that won’t heal: Oxygen-delivering technology can prevent amputations
As aging populations and rising diabetes rates drive an increase in chronic wounds, more patients face the risk of amputations. UC Riverside researchers have developed an oxygen-delivering gel capable of healing injuries that might otherwise progress to limb loss.
Injuries that fail to heal for more than a month are considered chronic wounds. They affect an estimated 12 million people annually worldwide, and around 4.5 million in the U.S. Of these, about one in five patients will ultimately require a life-altering amputation.
The new gel, tested in animal models, targets what researchers believe is a root cause of many chronic wounds: a lack of oxygen in the deepest layers of the damaged tissue. Without sufficient oxygen, wounds languish in a prolonged state of inflammation, allowing bacteria to flourish and tissue to deteriorate rather than regenerate.
Senescent cells after pregnancy may fuel postpartum breast cancer spread
Postpartum breast cancer is diagnosed five to ten years after giving birth. It is associated with a higher risk of metastasis and a lower survival rate compared with women who have not been pregnant or those diagnosed during pregnancy. A team from the Institut Pasteur set out to understand the mammary gland mechanisms involved in tumor formation during involution, a major tissue remodeling process that occurs after pregnancy.
In a preclinical study, the scientists revealed how senescence, a cellular response inducing stable cell cycle arrest, plays an ambivalent role during mammary gland involution. While it is crucial for the normal tissue remodeling process in the mammary gland, senescence can also be hijacked by tumor cells to help them spread. This discovery, published in Nature Aging on February 18, 2026, suggests that targeting senescent cells during mammary gland involution could reduce the risk of postpartum breast cancer.
