Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice.

Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice.

MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage.

Aging is accompanied by altered intercellular communication, deregulated metabolic function, and inflammation. Interventions that restore a youthful state delay or reverse these processes, prompting the search for systemic regulators of metabolic and immune homeostasis. Here we identify MANF, a secreted stress-response protein with immune modulatory properties, as an evolutionarily conserved regulator of systemic and in particular liver metabolic homeostasis.

mTORC1 Activation during Repeated Regeneration Impairs Somatic Stem Cell Maintenance.

The balance between self-renewal and differentiation ensures long-term maintenance of stem cell (SC) pools in regenerating epithelial tissues. This balance is challenged during periods of high regenerative pressure and is often compromised in aged animals. Here, we show that target of rapamycin (TOR) signaling is a key regulator of SC loss during repeated regenerative episodes.

The combination of lithium and l-Dopa/Carbidopa reduces MPTP-induced abnormal involuntary movements (AIMs) via calpain-1 inhibition in a mouse model: Relevance for Parkinson׳s disease therapy.

Lithium has recently been suggested to have neuroprotective effects in several models of neurodegenerative disease including Parkinson׳s disease (PD). Levodopa (l-Dopa) replacement therapy remains the most common and effective treatment for PD, although it induces the complication of l-Dopa induced dyskinesia after years of use. Here we examined the potential use of lithium in combination with l-Dopa/Carbidopa for both reducing MPTP-induced abnormal involuntary movements (AIMs) as well as protecting against cell death in MPTP-lesioned mice.

Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis.

Human cervix cancer is caused by high-risk human papillomaviruses encoding E6 and E7 oncoproteins, each of which alter function of distinct targets regulating the cell cycle, apoptosis, and differentiation. Here we determined the molecular contribution of E6 or E7 to neoplastic progression and malignant growth in a transgenic mouse model of cervical carcinogenesis. E7 increased proliferation and centrosome copy number, and produced progression to multifocal microinvasive cervical cancers.