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Mitochondrial Fusion and Fission in Age-Related Cardio-Cerebral Diseases: Mechanisms and Interventions
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...
Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice
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...
Motor Cortex Hyperexcitability Is Coupled to Neuromuscular Dysfunction in Aged Mice
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 Transplantation Rejuvenates Aging Heart by Restoring Mitophagy Flux via the HIF-3alpha-BNIP3 Axis
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....
Transplantation of Elderly Human Gut Microbiota Into Pigs Reprograms Intestinal Barrier Function, Plasma Metabolome, and Gut Mucosal Transcriptomic Landscape
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...
Associations Between Gut Microbiota and Immune Profiles in Community-Dwelling Older Adults and the Regulatory Role of Polygonatum odoratum
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...