By analyzing co-evolution of mitochondrial and nuclear genomes across insect species, the authors uncover the evolutionary covariation of a group of non-mitochondrially targeted nuclear genes with mitochondrial genes, including the uncharacterized gene CG11837, which regulates insect lifespan.
University of Queensland researchers have unlocked crucial molecular secrets of ageing in cells, potentially paving the way to improve quality of life as people age.
The study decoded the process by which genes regulate how people mature as they grow and age, and was led by Dr Christian Nefzger from UQ’s Institute for Molecular Bioscience with key contributions from Dr Ralph Patrick and Dr Marina Naval-Sanchez.
Dr Nefzger said that until now the process of how genes change activity from birth to adulthood and into old age was largely unknown.
Helping to defend those tissues are innate lymphoid cells, or ILCs, which when faced with a threat, stimulate proteins called cytokines that further activate the immune system and control the intestinal microbiome.
These cells naturally diminish with aging or can be depleted by certain medical conditions.
ILCs are made inside bone marrow and circulate in the blood. But how are they activated to mobilize and travel to their target sites to replenish the depleted pool of tissue ILCs?
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Increased frailty, higher incidence of diseases, and death. As the population grows older, there is a need to reveal mechanisms associated with aging that could spearhead treatments to postpone the onset of age-associated decline, extend both healthspan and lifespan. One possibility is targeting the sirtuin SIRT1, the founding member of the sirtuin family, a highly conserved family of histone deacetylases that have been linked to metabolism, stress response, protein synthesis, genomic instability, neurodegeneration, DNA damage repair, and inflammation. Importantly, sirtuins have also been implicated to promote health and lifespan extension, while their dysregulation has been linked to cancer, neurological processes, and heart disorders. SIRT1 is one of seven members of sirtuin family; each requiring nicotinamide adenine dinucleotide (NAD+) as co-substrate for their catalytic activity. Overexpression of yeast, worm, fly, and mice SIRT1 homologs extend lifespan in each animal, respectively. Moreover, lifespan extension due to calorie restriction are associated with increased sirtuin activity. These findings led to the search for a calorie restriction mimetic, which revealed the compound resveratrol; (3, 5, 4′-trihydroxy-trans-stilbene) belonging to the stilbenoids group of polyphenols. Following this finding, resveratrol and other sirtuin-activating compounds have been extensively studied for their ability to affect health and lifespan in a variety of species, including humans via clinical studies.
Aging is associated with a progressive metabolic, physiological decline and can be genetically and environmentally modified (Helfand and Rogina, 2000). The search for the molecular basis of aging led to the identification of several pathways associated with longevity including insulin/IGF-1, target of rapamycin (TOR) and the Sirtuins (Kenyon, 2010; Chen et al., 2022). The sirtuins are a family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases (Haigis and Sinclair, 2010; Hall et al., 2013; Bonkowski and Sinclair, 2016; Dai et al., 2018; Singh et al., 2018). Sirtuins are also categorized as deacetylases because they catalyze the post-translational modification of signaling molecules including decrotonylation, ADP-ribosylation, diacylation, desuccinylation, demalonylation, depropynylation, delipoamidation, and deglutarylation, and other long-chain fatty acid deacylations (Feldman, Baeza, and Denu, 2013; Choudhary et al., 2014; Fiorentino et al., 2022).
In mammals, there are seven members (SIRT1-SIRT7) including SIRT1, SIRT6 and SIRT7, which are localized to the nucleus, and SIRT3, SIRT4, and SIRT5 localized to the mitochondria, SIRT2 localized to the cytosol, and SIRT1 also localized to cytosol in some cell types (Bonkowski and Sinclair, 2016). As histone deacetylases, sirtuins function by removing acetyl groups from the target proteins resulting in either inhibition or activation. SIRT1, SIRT6 and SIRT7 have many functions including: regulators of transcription, control of cellular metabolism, DNA repair, cell survival, tissue regeneration, inflammation, circadian rhythms and neuronal signaling (Haigis and Sinclair, 2010). SIRT3-5 are important for switching to mitochondrial oxidative metabolism during CR and modulate stress tolerance (Verdin et al., 2010).
There are biological underpinnings to aging—and so researchers are investigating cell manipulations, transfusions of young blood, and chemical compounds that can mimic low-calorie diets.
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Camera, A., Tabetah, M., Castañeda, V. et al. Aging and putative frailty biomarkers are altered by spaceflight. Sci Rep 14, 13,098 (2024). https://doi.org/10.1038/s41598-024-57948-5
Petr Sramek, Co-founder of the Healthy Longevity Clinic, and Managing Partner of the LongevityTech.fund, presents at the Rejuvenation Startup Summit 2024.
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David is one of the world’s best-known philosophers of mind and thought leaders on consciousness. I was a freshman at the University of Toronto when I first read some of his work. Since then, Chalmers has been one of the few philosophers (together with Nick Bostrom) who has written and spoken publicly about the Matrix simulation argument and the technological singularity. (See, for example, David’s presentation at the 2009 Singularity Summit or read his The Singularity: A Philosophical Analysis)
During our conversation with David, we discuss topics such as: how and why Chalmers got interested in philosophy; and his search to answer what he considers to be some of the biggest questions – issues such as the nature of reality, consciousness, and artificial intelligence; the fact that academia in general and philosophy, in particular, doesn’t seem to engage technology; our chances of surviving the technological singularity; the importance of Watson, the Turing Test and other benchmarks on the way to the singularity; consciousness, recursive self-improvement, and artificial intelligence; the ever-shrinking of the domain of solely human expertise; mind uploading and what he calls the hard problem of consciousness; the usefulness of philosophy and ethics; religion, immortality, and life-extension; reverse engineering long-dead people such as Ray Kurzweil’s father.
As always you can listen to or download the audio file above or scroll down and watch the video interview in full. To show your support you can write a review on iTunes, make a direct donation, or become a patron on Patreon.
