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Study reignites debate over what, if anything, machines can feel

Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and...

Parkinson's disease (PD) is characterized by the accumulation of Lewy bodies (LBs) in the brain, predominantly consisting of aggregated and phosphorylated α-synuclein (α-Syn). Consequently, strategies to suppress α-Syn expression offer substantial therapeutic potential for PD. This study explores heteroduplex oligonucleotides (HDOs), an innovative gene-silencing technology utilizing DNA/RNA or DNA/DNA hybrids. We designed two HDOs targeting α-Syn: α-Syn-HDO-1 (DNA/RNA) and α-Syn-HDO-2 (DNA/DNA)....

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Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by pronounced clinical and molecular heterogeneity, as well as highly interconnected pathogenic pathways. This biological complexity has long hindered efforts to systematically define disease mechanisms and to develop effective, targeted therapies. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR) based functional...

Cellular senescence exerts powerful non-cell autonomous effects through the senescence-associated secretory phenotype (SASP). This SASP comprises soluble factors and extracellular vesicles (EVs). Although soluble SASP components can induce senescence in neighboring cells, the specific contribution of EVs to paracrine senescence is poorly defined. Here, we show that EVs released by senescent tumor cells are necessary and sufficient to propagate senescence. Conditioned media from bleomycin-induced...

Thymic involution, the age-related replacement of thymic soft tissue by fat, has been linked to immunosenescence and chronic inflammation, processes implicated in aging-associated comorbidities. Untreated HIV infection is associated with thymic atrophy and reduced thymic output. Although thymic function may normalize after initiation of antiretroviral therapy, the long-term consequences of HIV infection on thymic involution in people with HIV (PWH) remain unknown. We investigated whether thymic...

Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and...

Aging is a major risk factor for atherosclerosis and is accompanied by profound changes in the immune system, including effector T cell expansion, senescent cell accumulation, and increased pro-inflammatory signaling. Rapamycin, a promising rejuvenation therapeutic that inhibits mTORC1 and modulates immune aging, was investigated for its potential to attenuate pro-atherogenic immune responses in aged atherosclerotic mice. 80- to 90-week-old male Ldlr^(-/-) mice with established atherosclerotic...

Age-related weakness is strongly associated with disability and mortality in older adults. While muscle atrophy contributes to weakness, strength declines at a faster rate than muscle mass, implicating neural mechanisms such as changes at the spinal cord and neuromuscular junction. Yet, the role of the motor cortex in age-related weakness remains largely unexplored. We previously identified layer V pyramidal neurons (LVPNs) of the primary motor cortex as hyperexcitable in aged mice, but whether...

Mitochondrial quality control is severely impaired in the aging heart, largely attributed to disrupted mitophagy homeostasis. However, the key molecular drivers remain poorly defined, and the translational value of mitochondria-targeted therapy for cardiac aging is still underexplored. Here, we report prominent mitophagy flux congestion in aged cardiac tissue and confirm that mitochondrial transplantation efficiently rescues impaired mitophagy, ultimately rejuvenating the aging heart....

The gut microbiota plays a pivotal role in maintaining intestinal homeostasis and regulating host metabolism, yet its composition and function undergo substantial alterations with aging. However, the relationship between age-associated microbial changes and host intestinal physiology remains not fully elucidated. Here, we employed Bama miniature pigs, a model with close gastrointestinal similarity to humans, to investigate the impact of fecal microbiota transplantation (FMT) from young or...

Aging is often associated with intestinal microbiota imbalance and immune system degeneration. The dysregulation and crosstalk of these two factors markedly elevate the elderly's susceptibility to infections and age-related diseases. Polygonatum odoratum, a traditional Chinese medicinal herb, is widely used in geriatric care for its lung-moistening and nourishing effects. However, its potential regulatory roles on the microbiota and immunity in the aging context remain unreported. A total of 140...