Lifeboat Foundation

Growing evidence supports the antagonistic pleiotropy theory of mammalian aging. Accordingly, changes in gene expression following the pluripotency transition, and subsequent transitions such as the embryonic–fetal transition, while providing tumor suppressive and antiviral survival benefits also result in a loss of regenerative potential leading to age-related fibrosis and degenerative diseases. However, reprogramming somatic cells to pluripotency demonstrates the possibility of restoring telomerase and embryonic regeneration pathways and thus reversing the age-related decline in regenerative capacity. A unified model of aging and loss of regenerative potential is emerging that may ultimately be translated into new therapeutic approaches for establishing induced tissue regeneration and modulation of the embryo-onco phenotype of cancer.

Keywords:

• acetyl-CoA
• aging
• AMPK
• dietary restriction
• DNA methylation
• epigenetics
• mTOR
• pluripotent stem cells
• regeneration

Aging is often defined as a progressive deterioration of an organism over time, wherein the risk of mortality increases exponentially with age in the postreproductive years. Although everyday environmental risks from predation or infectious disease (e.g., stochastic risks) necessarily lead to increased mortality over time, they are not considered core to the definition of the aging process per se [1,2]. Thus, an important criterion of aging is that it encompasses virtually every somatic tissue type, including the gonads (though not necessarily the germ-line cells themselves, given their role in potentially perpetuating the species) [3]. In order to distinguish the aging process from damage that occurs stochastically over time, Benjamin Gompertz described aging as a process leading to an exponential increase in mortality with time, that is, R_m = R₀e^at where ‘R_m’ represents the probability of mortality between ages ‘t’ and ‘t + 1’.

Taken from JRE #1349 w/David Sinclair:

https://www.youtube.com/watch?v=ZGLL77wYxe8

In the version of evolutionary theory most of us are familiar with, randomly occurring variation in traits, caused by mutations in our DNA, can be fixed in a population through natural selection. However, writing in Epigenetics journal, a team of Swedish researchers from Linköping University suggests that mutations that can be caused by environmental changes, not just random chance, might be responsible for species diversity.

Until quite recently, it was assumed that DNA mutations causing new gene variations occurred more or less randomly. While random mutations do occur, recent research has shown that genes can be altered by environmental influences too. According to a study published in Epigenetics journal, a particular type of mutation, linked to epigenetic changes, has, over time, led to new animal breeds—and could be responsible for whole new species.

Dr. David Sinclair, a Professor of Genetics at Harvard Medical School, is one of the most well-known researchers in the field of rejuvenation, and his lab is the beneficiary of a successful Lifespan.io campaign.

Today, Dr. Sinclair is releasing his book on Amazon, “Lifespan: Why We Age and Why We Don’t Have To”, and on Wednesday, September 18, we will be hosting a webinar with Dr. Sinclair as well. Please contact [email protected] if you would like to join or have any questions regarding this webinar.

At International Perspectives in Geroscience, a conference hosted at Weizmann Institute of Science (Israel) on September 4–5, we had the opportunity to interview Dr. Sinclair about his work and his thoughts on the current state of research.

Bioengineers and life scientists incorporate hybridoma technology to produce large numbers of identical antibodies, and develop new antibody therapeutics and diagnostics. Recent preclinical and clinical studies on the technology highlight the importance of antibody isotypes for therapeutic efficacy. In a new study, a research team in Netherlands have developed a versatile Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) and homology directed repair (HDR) platform to rapidly engineer immunoglobin domains and form recombinant hybridomas that secrete designer antibodies of a preferred format, species or isotype. In the study, Johan M. S. van der Schoot and colleagues at the interdisciplinary departments of immunology, proteomics, immunohematology, translational immunology and medical oncology, used the platform to form recombinant hybridomas, chimeras and mutants. The stable antibody products retained their antigen specificity. The research team believes the versatile platform will facilitate mass-scale antibody engineering for the scientific community to empower preclinical antibody research. The work is now published on Science Advances.

Monoclonal antibodies (mAb) have revolutionized the medical field with applications to treat diseases that were once deemed incurable. Hybridoma technology is widely used since 1975 for mAb discovery, screening and production, as immortal cell lines that can produce large quantities of mAbs for new antibody-based therapies. Scientists had generated, validated and facilitated a large number of hybridomas in the past decade for preclinical research, where the mAb format and isotypes were important to understand their performance in preclinical models. Genetically engineered mAbs are typically produced with recombinant technology, where the variable domains should be sequenced, cloned into plasmids and expressed in transient systems. These processes are time-consuming, challenging and expensive, leading to outsourced work at contract research companies, which hamper the process of academic early-stage antibody development and preclinical research.

In its mechanism of action, the constant antibody domains forming the fragment crystallizable – (Fc) domain are central to the therapeutic efficacy of mAbs since they engage with specific Fc receptors (FcRs). Preceding research work had highlighted the central role of Fc in antibody-based therapeutics to emphasize this role. Since its advent, CRISPR and associated protein Cas-9 (CRISPR-Cas9)-targeted genome editing technology has opened multitudes of exciting opportunities for gene therapy, immunotherapy and bioengineering. Researchers had used CRISPR-Cas9 to modulate mAb expression in hybridomas, generate a hybridoma platform and engineer hybridomas to introduce antibody modification. However, a platform for versatile and effective Fc substitution from foreign species within hybridomas with constant domains remains to be genetically engineered.

While trying to regenerate the thymus gland, University of California, Los Angeles (UCLA) researchers might have found a solution to not only slowing down the ageing problem but actually reversing it, a new study claims.

Scientists volunteers in a California study were given a cocktail of three common drugs for one year- a growth hormone and two diabetes medications in order to stimulate the regeneration of thymus gland. However, according to a study published in Nature journal, researchers found that participants had lost an average of 2.5 years on their “epigenetic clock,” measured by analyzing marks on a person’s genomes.

“I’d expected to see slowing down of the clock, but not a reversal,” UCLA researcher Steve Horvath told Nature. “That felt kind of futuristic.”

In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’, which tracks a person’s biological age.

The average North American life – which values gregarious personalities, extroverted social styles, clamorous entertainment, bright lights and big sound – is simply too much for many sensitive people.

“This world is not built for sensitive people. In fact, our world is designed perfectly for those who are detached,” wrote Nicole Hollingshead, a Canadian empowerment blogger, in response to a Quora question about the highly sensitive person (HSP) trait. Her statement illustrates the way that most HSPs feel when comparing themselves to their seemingly unfazed non-HSP peers.

The term highly sensitive person was coined in the 1990s by husband and wife psychologist team Elaine Aron and Arthur Aron. The HSP trait is synonymous with the term sensory processing sensitivity (SPS) and is thought to be genetically determined and present at birth. SPS exists in 15–20 percent of the human population, and has been observed in over 100 nonhuman species.

Yesterday, the TRIIM study was described in science news headlines around the world, though, through a glitch, the original research paper is not yet on the Aging Cell web site. (You saw it first here.) I refer you to the writeup in Nature’s News section for a full summary of the paper, and in this column I will add my personal framing, and what I know about the study from private connection to its authors and one of the subjects. The big news is setback of the epigenetic clock, by several methylation measures. Instead of getting a year older during the trial, nine subjects got a year younger, on average, based on the version of the Horvath methylation clock that best predicts lifespan. The study had been originally designed to regrow the thymus. (Loss of thymus function has been linked to the collapse of the immune system that occurs typically before age 70.) Imaging showed that the functional part of the thymus expanded over the course of the trial, and blood tests confirmed improved immune function. The treatment included.