Lifeboat Foundation

A team of researchers, including Dr. David Sinclair, has recently made a new study available as a preprint prior to peer review and publication in the journal Cell.

DNA damage and the double-strand break

Two of the primary hallmarks of aging are genomic instability, which consists of damage to our DNA, and epigenetic alterations, which are the changes in gene expression that occur with aging and are harmful to normal cell function.

Circulating levels of white blood cells (WBCs) are one of the 10 variables used to quantify biological age with PhenoAge (https://michaellustgarten.com/2019/09/09/quantifying-biological-age). The reference range for WBCs is 4.5 – 11 *10⁹ cells/L, but within that range, what’s optimal?

Several studies have reported that WBCs greater than 5 are associated with an increased all-cause mortality risk (Ahmadi-Abhari et al. 2013, Samet et al. 2005, Weijenberg et al. 1996). While observational studies are important for identifying associations with mortality risk, stronger evidence is obtained when the data from the same subjects are tracked for a time period. Perhaps the best evidence for the association between WBCs with mortality risk comes from the Baltimore Longitudinal Study on Aging (BLSA), which studied 2803 men and women over a period of 44 years (Ruggiero et al. 2007). As shown below, subjects that had circulating WBCs between 3.5 – 6 had the best survival, whereas WBCs below 3.5, between 6 – 10, and 10+ each had successively higher risk. The 0.5 point on the y-axis of the curve (survival) is defined as 50% mortality, and is the point where half of the study subjects died, whereas the remaining 50% were still alive.

A supposedly rare genetic quirk might be more common than we think, according to new research out Thursday. The study, based largely on 23andMe data, suggests that one in every 2,000 people are born with two copies of a gene from only a single parent, often with no serious health consequences.

Ordinarily, a person’s egg or sperm cells have one set of the genes that make up their chromosomes (other cells in our body have two sets). When a sperm fertilizes an egg, the resulting fertilized zygote will then have two sets of 23 chromosomes, one from each parent, making 46 chromosomes in total. If all goes well, the zygote multiplies and divides until it becomes a person, one with an even allocation of gene copies from both parents.

Many of the world’s most common or deadly human pathogens are RNA-based viruses—Ebola, Zika and flu, for example—and most have no FDA-approved treatments. A team led by researchers at the Broad Institute of MIT and Harvard has now turned a CRISPR RNA-cutting enzyme into an antiviral that can be programmed to detect and destroy RNA-based viruses in human cells.

Researchers have previously adapted the Cas13 enzyme as a tool to cut and edit human RNA and as a diagnostic to detect the presence of viruses, bacteria, or other targets. This study is one of the first to harness Cas13, or any CRISPR system, as an antiviral in cultured human cells.

The researchers combined Cas13’s antiviral activity with its diagnostic capability to create a single system that may one day be used to both diagnose and treat a viral infection, including infections caused by new and emerging viruses. Their system, called CARVER (Cas13-Assisted Restriction of Viral Expression and Readout), is described today in Molecular Cell.

Aim: Aging in humans is associated with a 10–40-fold greater incidence of sudden cardiac death from malignant tachyarrhythmia. We have reported that thiol oxidation of ryanodine receptors (RyR2s) by mitochondria-derived reactive oxygen species (mito-ROS) contributes to defective Ca²⁺ homeostasis in cardiomyocytes (CMs) from aging rabbit hearts. However, mechanisms responsible for the increase in mito-ROS in the aging heart remain poorly understood. Here we test the hypothesis that age-associated decrease in autophagy is a major contributor to enhanced mito-ROS production and thereby pro-arrhythmic disturbances in Ca²⁺ homeostasis.

Methods and Results: Ventricular tissues from aged rabbits displayed significant downregulation of proteins involved in mitochondrial autophagy compared with tissues from young controls. Blocking autophagy with chloroquine increased total ROS production in primary rabbit CMs and mito-ROS production in HL-1 CMs. Furthermore, chloroquine treatment of HL-1 cells depolarized mitochondrial membrane potential (Δψm) to 50% that of controls. Blocking autophagy significantly increased oxidation of RyR2, resulting in enhanced propensity to pro-arrhythmic spontaneous Ca²⁺ release under β-adrenergic stimulation. Aberrant Ca²⁺ release was abolished by treatment with the mito-ROS scavenger mito-TEMPO. Importantly, the autophagy enhancer Torin1 and ATG7 overexpression reduced the rate of mito-ROS production and restored both Δψm and defective Ca²⁺ handling in CMs derived from aged rabbit hearts.

Conclusion: Decreased autophagy is a major cause of increased mito-ROS production in the aging heart. Our data suggest that promoting autophagy may reduce pathologic mito-ROS during normal aging and reduce pro-arrhythmic spontaneous Ca²⁺ release via oxidized RyR2s.

Back in January, we were joined by Dr. Aubrey de Grey, Dr. Amutha Boominathan, Dr. Matthew O’Conner, and Michael Rae from the SENS Research Foundation for a webinar discussion panel focused on MitoSENS, the mitochondrial repair program. During the webinar, a number of points were discussed, and the Lifespan Heroes in the audience got to ask the researchers questions about MitoSENS and about the work of the SENS Foundation in general.

In 2015, the MitoSENS team raised funding on Lifespan.io to launch a study testing if they could create mitochondrial DNA copies in the cell nucleus, and they were successful in doing so as a result of the funds they received. In October 2019, the MitoSENS team launched a new follow-up project called MitoMouse, which aims to bring its mitochondrial repair therapy to mammals as a proof of concept on the road to translation to human use.

Many of us are fascinated by our various computing devices — our smartphones, our smart watches, and an ever-growing array of smart devices. What we sometimes forget is that we are biological creatures (at least, until The Singularity), and that even though biology as a discipline has been around much longer than computing, biology may yet supersede it.

If the 20th century was the era of computers, the 21st century may be the era of biology. And the two may even merge. Hello, synthetic biology and biological computing!

Last week SynBioBeta hosted The Global Synthetic Biology Summit, “where tech meets bio and bio meets tech.” People were urged to attend “to see how synthetic biology is disrupting consumer products, food, agriculture, medicine, chemicals, materials, and more.”

I’m excited to share I did an interview on transhumanism with Skyy John of Tipsy Bartender. He’s an actor and one the most famous people in the alcohol business!

We are about to live FOREVER because of new advances in technology and artificial intelligence! I sat down with futurist and transhumanist Zoltan Istvan as he explains how all of this will happen.

Continue reading “Can Artificial Intelligence upgrade the human body? — featuring Zoltan Istvan” »

https://www.lifespan.io/mitomouse

We would like to give our most heartfelt thanks to John Saunders and the other wonderful donors in the last few days who have helped us get ever closer to the intial project goal of 50k.