Reactive oxygen species (ROS) of mitochondrial origin are putatively involved in cellular senescence. The long-lived naked mole rat is similar in size to the common mouse, but lives >30 years instead of >3 years. We found that, as opposed to a long-standing hypothesis, this long-lived species is not characterized by lower rate of mitochondrial ROS formation. Instead detoxification of a key ROS species (H₂O₂) proceeds much faster in mitochondria of this species.

A short-term starvation (STS) treatment in young adult male Caenorhabditis elegans significantly improves their reproduction fitness when they are aged. STS stress preserves sperm number and quality in aged male worms, and the mechanism underlying requires anaphase-promoting complex/cyclosome (APC/C) activity crucial for meiotic division to produce sperms. STS-induced hormetic effects prevent the age-associated decline of FZY-1/CDC-20 expression, which in turn maintains APC/C activity from decline with age.

The loss of cholesterol from the plasma membrane of hippocampal neurons during aging causes changes in membrane fluidity affecting different signaling pathways. In particular, we observed a tonic insulin and IGF-1 receptor activation in the raft fractions of the membrane of old neurons, in a cholesterol loss-dependent manner. The sustained activity of receptor signaling leads little by little to final pathway desensitization, affecting insulin-dependent synaptic functions (insulin-LTD) and in the end optimal neuronal performance.

Aged mesenchymal stromal cells (MSC) display early senescence features including SA-β-Gal accumulation, DDR, and SASP activation. Through SASP, aged MSC impair the clonogenic potential of hematopoietic stem and progenitor cells (HSPC) and induce the activation of a pro-inflammatory transcriptional program in young HSPC.

Ubiquitous progerin expression causes decreased smooth muscle tissue content and increased collagen deposition in the media associated with inward remodeling and vessel stiffness. These alterations are reproduced in mice expressing progerin in vascular smooth muscle cells but not in endothelial cells. Treatment with nitrites prevents progerin-induced inward remodeling and vessel stiffness.

Upregulation of ALCAT1 by MPTP-induced α-synucleinopathy and oxidative stress promotes cardiolipin peroxidation, leading to impaired mitochondrial fusion and mitophagy which trigger the onset of neurodegenerative diseases

How the inflammatory cytokine IL-1α is activated is not well defined. Wiggins et al show that the inflammatory human caspase-5 and mouse caspase-11 directly cleave and activate pro-IL-1α. Intracellular LPS (icLPS) activates caspase-5/-11 in macrophages, leading to release of cleaved IL-1α. Importantly, caspase-5/-11-cleaved pro-IL-1α drives the senescence-associated secretory phenotype (SASP), leading to immune-mediated clearance of senescent cells in vivo.

Impaired plasticity of subcutaneous white adipose tissue (scWAT) contributes to insulin resistance during aging, which is already evident in middle-aged mice. Alteration of thyroid axis status with age is an important factor contributing to BAT dysfunction in middle-aged animals. Defects in WAT and BAT/beige cells during aging are ameliorated by long-term caloric restriction (CR).

1,25(OH)₂D₃ deficiency results in increasing oxidative stress through inhibiting transcription of Nrf2 and enhancing DNA damage; in addition, activation of p16/Rb and p53/p21 signaling occurs. These events then lead to inhibition of cellular proliferation and induction of cellular senescence and SASP, and thus acceleration of aging. These processes may be rescued to different degrees and aging postponed by supplementation of exogenous 1,25(OH)₂D₃, calcium/phosphate alone or combined calcium/phosphate and antioxidant NAC, or knockdown of p53 or knockout of p16.

Obesity induces the formation of senescent cells, which contribute to inflammation, insulin resistance, and organ dysfunction. Senescent cell clearance may be an effective strategy for alleviating important elements of obesity-related metabolic dysfunction.

Loss of NAD+ content and NMNAT2 protein results in the meiotic abnormalities and metabolic dysfunction in oocytes from old mouse. NA supplement and SIRT1 overexpression/activation could partly rescue the defective phenotype of these aged oocytes.

A summary of the molecular pathways responsible for the protective role of IGF-1 isoforms against sarcopenia.

Aging and the accumulation of senescence promote adverse cardiac remodelling and fibrosis. In the event of a myocardial infarction (MI), aged mice demonstrate reduced cardiac function and high mortality. Treatment of aged mice with the senolytic navitoclax alleviated adverse myocardial remodelling, improved the maintenance of cardiac function and increased survival following MI.

We tested the role of hyperadrenocorticism in the anti-inflammatory action of calorie restriction (CR), using a corticosterone (CORT)-deficient knockout (KO) mouse. The reduced inflammation of CR wild-type (WT) mice was blocked in CR KO mice. Replacement of CORT in CR KO mice to the elevated levels of CR WT mice (but not to the lower levels of ad lib fed mice) rescued the anti-inflammatory action of CR—indicating that the hyperadrenocorticism of CR contributes to its anti-inflammatory action.

Genetic variations in the enhancer-like regions downstream of the Cyp24a1 gene regulate its basal expression in different strains of inbred mice. Deletions and substitutions in the putative Cyp24a1 regulatory sequences in susceptible C3H, BALB/c, and 129 mice lead to reduced basal expression of the gene, compared to resistant C57BL/6 mice, and render susceptible strains to the aging-related detrimental phenotypes with decreased Klotho expression.

Recent reports by Martincorena et al and Yokoyama et al reveal unanticipated dynamics of somatic evolution in the esophageal epithelium, with clonal expansions apparently driven by mutations in Notch1 dominating the epithelium even in middle-aged individuals, far outpacing the prevalence of these mutations in esophageal cancers. We propose a model whereby the promotion of clonal expansions by mutations such as in Notch1 can limit more malignant somatic evolutionary trajectories until old ages.