The free radical theory of aging proposes that reactive oxygen species (ROS)-induced accumulation of damage to cellular macromolecules is a primary driving force of aging and a major determinant of lifespan. Although this theory is one of the most popular explanations for the cause of aging, several experimental rodent models of antioxidant manipulation have failed to affect lifespan. Moreover, antioxidant supplementation clinical trials have been largely disappointing. The mitochondrial theory of aging specifies more particularly that mitochondria are both the primary sources of ROS and the primary targets of ROS damage. In addition to effects on lifespan and aging, mitochondrial ROS have been shown to play a central role in healthspan of many vital organ systems. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and dysfunction in aging and healthspan, including cardiac aging, age-dependent cardiovascular diseases, skeletal muscle aging, neurodegenerative diseases, insulin resistance and diabetes as well as age-related cancers. The crosstalk of mitochondrial ROS, redox, and other cellular signaling is briefly presented. Potential therapeutic strategies to improve mitochondrial function in aging and healthspan are reviewed, with a focus on mitochondrial protective drugs, such as the mitochondrial antioxidants MitoQ, SkQ1, and the mitochondrial protective peptide SS-31.

Myiasis is the infestation of tissue by the larvae of flies. We report eight cases of human myiasis in Hong Kong. All patients were nursing home residents with an average age of 81.8 years. Seven patients were bedridden with advanced dementia. Four patients had pre-existing wounds. Five had poor oral hygiene and four of those were on tube feeding. All of the five patients with poor oral hygiene suffered from oral myiasis. Two patients had vaginal infestations and one had wound myiasis in his diabetic foot ulcer. Seven cases were infested by Chrysomya bezziana, an obligatory parasite that requires living mammalian tissue for its larval development. Larvae of the Calliphoridae family were responsible for the remaining case. Patients were managed with manual removal of larvae and irrigation of the site of infestation with saline. All infestations were nosocomial, being acquired in nursing homes. Carers of the old and debilitated should be made aware of the need for better oral care, especially for those on tube feeding. The use of window screens in nursing homes should be encouraged to reduce the chance of flies entering the vicinity of these patients. Electrocuters could also be mounted indoors to kill flies that do enter.

TFEB promotes lysosomal biogenesis, autophagy, and lysosomal exocytosis. The present study characterized the consequence of inducible TFEB overexpression in cardiomyocytes in vivo. We generated cardiomyocyte-specific doxycycline inducible (Tet off) mice to achieve spatial and temporal control of TFEB overexpression, by crossing TFEB transgenic mice with mice harboring the tTA transgene (TFEB/tTA). Two weeks after doxycycline removal, an 8-fold increase in TFEB protein expression was observed in transgenic hearts. Heart weight normalized to tibia length was increased by 2.5-fold following TFEB overexpression (TFEB/tTA), characterized by induction of markers of pathological hypertrophy, such as Nppa, Nppb and Acta1, progressive contractile dysfunction and cardiac dilatation. Overexpression of TFEB resulted in premature death, associated with high degree AV block. Reversal of TFEB overexpression normalized cardiac structure and function. Mitochondrial respiration and ATP levels were preserved after 2-weeks of TFEB induction, despite reduced mitochondrial (OXPHOS) protein expression, mtDNA content, and altered mitochondrial morphology. Signaling through mTOR was induced in TFEB/tTA mice, and when inhibited by rapamycin treatment for 4 weeks, partially offset left ventricular dysfunction. Transcriptome analysis revealed early suppression of mitochondrial metabolic pathways, induction of fibrosis and altered calcium signaling. MCOLN1, a lysosomal calcium release channel, the calcineurin target RCAN1.4, and the mitochondrial calcium uniporter (MCU) were strikingly induced in TFEB/tTA mice. In summary, persistent overexpression of TFEB in cardiomyocytes promotes pathologic cardiac hypertrophy via suppression of mitochondrial bioenergetic pathways and activation of pro-fibrotic and calcium regulatory pathways.

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