Davide D’Amico: Mitochondrial autophagy
We associate getting older with a loss of energy. On the molecular level, this is quite literally true, because one of the hallmarks of aging is mitochondrial dysfunction. Mitochondria are often referred to as “the powerhouse of the cell,” because they convert nutrients from the food we eat into usable energy, in the form of ATP. But as we age, mitochondria become less effective at generating the energy we need for various chemical processes.
So why does this happen? As with most things in biology, there are definitely multiple factors at work here. But one likely reason is a failure of quality control. As we age, mitochondrial autophagy (aka mitophagy) declines, and our body starts to accumulate broken and dysfunctional mitochondria. This becomes most obvious in tissues that consume a lot of energy, like skeletal muscle. Hence, mitochondrial dysfunction is linked to poor muscular strength in older people. If we could find a way to ramp up mitophagy, perhaps we could retain excellent mitochondrial function throughout our golden years.
In this episode of humanOS Radio, Dan Pardi welcomes Dr. Davide D’Amico to the show. Davide is a research scientist in the field of metabolism and aging. He was previously a post-doc at the Auwerx Laboratory of Integrative Systems Physiology at the École Polytechnique Fédérale de Lausanne (EPFL), where he investigated the role of mitochondrial function in health, disease, and the aging process.
Neural networks and deep learning
Artificial neural networks are better than other methods for more complicated tasks like image recognition, and the key to their success is their hidden layers. We’ll talk about how the math of these networks work and how using many hidden layers allows us to do deep learning. Neural networks are really powerful at finding patterns in data which is why they’ve become one of the most dominant machine learning technologies used today.
Rapamycin (Sirolimus) slows aging, extends life span, and prevents age-related diseases, including diabetic complications such as retinopathy. Puzzlingly, rapamycin can induce insulin sensitivity, but may also induce insulin resistance or glucose intolerance without insulin resistance. This mirrors the effect of fasting and very low calorie diets, which improve insulin sensitivity and reverse type 2 diabetes, but also can cause a form of glucose intolerance known as benevolent pseudo-diabetes.
There is no indication that starvation (benevolent) pseudo-diabetes is detrimental. By contrast, it is associated with better health and life extension.
In transplant patients, a weak association between rapamycin/everolimus use and hyperglycemia is mostly due to a drug interaction with calcineurin inhibitors. When it occurs in cancer patients, the hyperglycemia is mild and reversible. No hyperglycemic effects of rapamycin/everolimus have been detected in healthy people.
For antiaging purposes, rapamycin/everolimus can be administrated intermittently (e.g., once a week) in combination with intermittent carbohydrate restriction, physical exercise, and metformin.
We’re living longer than ever before. But are we living better? Scientists are developing new medicines designed to reverse ageing. These drugs seek out and destroy the ‘sleeping cells’ that cause inflammation – a major driver for age-related disease. Neuroscientist Dr Sarah McKay uncovers this extraordinary new science, by speaking to Prof Judith Campisi and Prof Simon Melov at the Buck Institute.
Among the existing growth factors, we highlight the fibroblast growth factor (FGF), which induces the synthesis of type 1 collagen and therefore presents a relevant role in the process of skin aging control. Collagen is the protein responsible for the structure, elasticity, and firmness of the skin and it is produced by cells called fibroblasts. During the aging process, the proliferative and metabolic activity of fibroblasts decreases and their functions are impaired, leading to reduction of the synthesis of structural substances such as collagen, elastin, hyaluronic acid, and chondroitin. In addition, decreased levels of growth factors, reduced amount of collagen, abnormal accumulation of elastin, and reduction in the epidermal and dermal thickness were observed during the aging process.
The FGF family members increase the proliferation and activation of fibroblasts by stimulating the accumulation of collagen as well as stimulating endothelial cell division. With the aging process, fibroblasts have their activity diminished and consequently the synthesis and activity of proteins that guarantee elasticity and resistance such as elastin and collagen are also affected. Thus, in aged skin, there is a lower production of collagen by the fibroblasts and a greater action of the enzymes that degrade it. This lack of balance speeds up the aging process. Although the functions of FGFs are well characterized, their mechanisms of action are still not completely clear. It is known that it involves inter- and extracellular signaling pathways that may be related to the RAS-MAP kinases pathways, PI3K–AKT, PLC-γ, or STAT. Therefore, FGF cell signaling involves interactions with multiple cell signaling pathways and complex feedback mechanisms.
Activation of FGF-1 improves skin elasticity and induces the synthesis of collagen and elastin. One study investigated the impact of FGF-1 on skin cells; results showed that recombinant FGF-1 has a strong effect on cellular proliferation of keratinocytes and fibroblasts. FGF-2 reduces and prevents expression lines and wrinkles through the activation of new skin cells and stimulates the proliferation of cells of mesodermal, ectodermal, and endodermal origin, mainly fibroblasts and keratinocytes. Researchers aimed to evaluate an in vivo method for aged skin rejuvenation through direct injection of intradermal FGF-2. The following rejuvenating effects were observed: improvement of skin smoothness, atrophied skin thickness, and improved viscoelasticity. Keratinocyte growth factor (KGF) is a member of the FGF family. While most FGFs influence the proliferation and/or differentiation of various cell types, KGF appears to act specifically on epithelial cells. A study evaluating the ability of KGF to reduce the visible signs of aging. The results showed that eighteen of the twenty subjects experienced significant improvement.