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Abstract. Pharmacological inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway with rapamycin can extend lifespan in several organisms. Although this includes the nematode Caenorhabditis elegans, effects in this species are relatively weak and sometimes difficult to reproduce. Here we test effects of drug dosage and timing of delivery to establish the upper limits of its capacity to extend life, and investigate drug effects on age-related pathology and causes of mortality. Liposome-mediated rapamycin treatment throughout adulthood showed a dose-dependent effect, causing a maximal 21.9% increase in mean lifespan, but shortening of lifespan at the highest dose, suggesting drug toxicity. Rapamycin treatment of larvae delayed development, weakly reduced fertility and modestly extended lifespan. By contrast, treatment initiated later in life robustly increased lifespan, even from Day 16 (or ~70 years in human terms). The rapalog temsirolimus extended lifespan similarly to rapamycin, but effects of everolimus were weaker. As in mouse, rapamycin had mixed effects on age-related pathologies, inhibiting one (uterine tumor growth) but not several others, suggesting a segmental antigeroid effect. These findings should usefully inform future experimental studies with rapamycin and rapalogs in C. elegans.

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Research in mice shows limited intakes of one particular essential amino acid can slow the impacts of aging and even lengthen their lifespan.

Scientists are now wondering if these findings could help people improve their longevity and quality of life.

Isoleucine is one of three branched-chain amino acids we use to build proteins in our bodies. It is essential for our survival, but since our cells can’t produce it from scratch, we have to get it from sources like eggs, dairy, soy protein, and meats.

Scientists from the Longevity Research Institute (LRI), which was formed by the merger of SENS Research Foundation and Lifespan.io, have achieved expression of an essential mitochondrial gene in the nucleus and proper functioning of the protein. This could pave the way for curing diseases caused by mitochondrial mutations [1].

The fragile mitochondrial DNA

The prevailing scientific consensus is that mitochondria were once independent microorganisms that entered a symbiotic relationship with larger cells. This duo gave rise to eukaryotic cells: the building blocks of all multicellular life. Without that fateful “marriage,” complex life would not exist, as mitochondria provide cells with essential energy via oxidative phosphorylation.

Major findings on the inner workings of a brittle star’s ability to reversibly control the pliability of its tissues will help researchers solve the puzzle of mutable collagenous tissue (MCT) and potentially inspire new “smart” biomaterials for human health applications.

The work is directed by Denis Jacob Machado—assistant professor in Bioinformatics at The University of North Carolina at Charlotte Center for Computational Intelligence to Predict Health and Environmental Risks (CIPHER)—and Vladimir Mashanov, staff scientist at Wake Forest Institute for Regenerative Medicine.

In “Unveiling putative modulators of mutable collagenous tissue in the brittle star Ophiomastix wendtii: an RNA-Seq analysis,” published recently in BMC Genomics, the researchers describe using advanced transmission electron microscopy (TEM), RNA sequencing, and other bioinformatics methods to identify 16 potential MCT modulator genes. This research offers a breakthrough towards understanding precisely how echinoderms quickly and drastically transform their collagenous tissue. The first author of the paper, Reyhaneh Nouri, is a Ph.D. student in UNC Charlotte’s Department of Bioinformatics and Genomics.

Chaperone-mediated autophagy (CMA) is the lysosomal degradation of individually selected proteins, independent of vesicle fusion. CMA is a central part of the proteostasis network in vertebrate cells. However, CMA is also a negative regulator of anabolism, and it degrades enzymes required for glycolysis, de novo lipogenesis, and translation at the cytoplasmic ribosome. Recently, CMA has gained attention as a possible modulator of rodent aging. Two mechanistic models have been proposed to explain the relationship between CMA and aging in mice. Both of these models are backed by experimental data, and they are not mutually exclusionary. Model 1, the “Longevity Model,” states that lifespan-extending interventions that decrease signaling through the INS/IGF1 signaling axis also increase CMA, which degrades (and thereby reduces the abundance of) several proteins that negatively regulate vertebrate lifespan, such as MYC, NLRP3, ACLY, and ACSS2. Therefore, enhanced CMA, in early and midlife, is hypothesized to slow the aging process. Model 2, the “Aging Model,” states that changes in lysosomal membrane dynamics with age lead to age-related losses in the essential CMA component LAMP2A, which in turn reduces CMA, contributes to age-related proteostasis collapse, and leads to overaccumulation of proteins that contribute to age-related diseases, such as Alzheimer’s disease, Parkinson’s disease, cancer, atherosclerosis, and sterile inflammation. The objective of this review paper is to comprehensively describe the data in support of both of these explanatory models, and to discuss the strengths and limitations of each.

Chaperone-mediated autophagy (CMA) is a highly selective form of lysosomal proteolysis, where proteins bearing consensus motifs are individually selected for lysosomal degradation (Dice, 1990; Cuervo and Dice, 1996; Cuervo et al., 1997). CMA is mechanistically distinct from macroautophagy and microautophagy, which, along with CMA, are present in most mammalian cells types.

Macroautophagy (Figure 1 A) begins when inclusion membranes (phagophores) engulf large swaths of cytoplasm or organelles, and then seal to form double-membrane autophagosomes. Autophagosomes then fuse with lysosomes, delivering their contents for degradation by lysosomal hydrolases (Galluzzi et al., 2017). Macroautophagy was the first branch of autophagy to be discovered, and it is easily recognized in electron micrograms, based on the morphology of phagophores, autophagosomes, and lysosomes (Galluzzi et al., 2017).

Scientists have identified previously unreported genes which appear to play a key role in the muscle ageing process.

It is hoped that the findings from the Nottingham Trent University study could be used to help delay the impact of the ageing process.

Muscle ageing is a natural process which occurs in everyone, causing people to lose muscle mass, strength and endurance as they get older – and is linked to increasing falls and physical disabilities.

A recent study investigates the relationship between exercise and the expression of MYC in skeletal muscles over time, revealing that even minimal doses can promote muscle growth without physical activity.

Researchers have long known that there is a relationship between the cancer-associated gene MYC (pronounced “Mick”) and exercise adaptation. When human muscles are exercised, MYC is found to increase transiently in abundance over 24 hours. But as we age, the MYC response to exercise is blunted, perhaps explaining a reduced ability to recover from exercise and maintain or gain muscle.

Knowing the precise mechanisms by which MYC drives muscle growth could prove instrumental in creating therapies that reduce muscle loss from aging, potentially improving independence, mobility, and health.