Most the events of the past year relating to longevity science were held virtually, thanks to the ongoing pandemic and the reaction to it. Here find notes and presentation video from the Aging, Geroscience and Longevity Symposium that was held last year, discussing an eclectic selection of research into aging and the treatment of aging.
Biological aging is the greatest risk factor for nearly every major cause of death and disability in developed countries, and new insights into the aging process may fundamentally change the way we approach human health. From basic research on the cellular and molecular hallmarks of aging to the next generation of "aging clocks" to potential clinical interventions, watching back the symposium recording presents an opportunity to hear the very latest from scientists in this field.
From Peter Fedichev of GERO: Heritability of human lifespan is 23-33% as evident from twin studies. Genome-wide association studies explored this question by linking particular alleles to lifespan traits. However, genetic variants identified so far can explain only a small fraction of lifespan heritability in humans. Here, we report that the burden of rarest protein-truncating variants (PTVs) in two large cohorts is negatively associated with human healthspan and lifespan, accounting for 0.4 and 1.3 years of their variability, respectively. In addition, longer-living individuals possess both fewer rarest PTVs and less damaging PTVs. We further estimated that somatic accumulation of PTVs accounts for only a small fraction of mortality and morbidity acceleration and hence is unlikely to be causal in aging. We conclude that rare damaging mutations, both inherited and accumulated throughout life, contribute to the aging process, and that burden of ultra-rare variants in combination with common alleles better explain apparent heritability of human lifespan.
From Hosni Cherif of McGill University: Intervertebral disc (IVDs) degeneration is one of the major causes of back pain. Cellular senescence is a state of stable cell cycle arrest in response to a variety of cellular stresses including oxidative stress and DNA damage. The accumulation of senescent IVD cells in the tissue suggest a crucial role in the initiation and development of painful IVD degeneration. Senescent cells secrete an array of cytokines, chemokines, growth factors, and proteases known as the senescence-associated secretory phenotype (SASP). The SASP promote matrix catabolism and inflammation in IVDs thereby accelerating the process of degeneration. This study demonstrates the potential of a natural (o-Vanillin) and a synthetic (RG-7112) senolytic compounds to remove senescent IVD cells, decrease SASP factors release, reduce the inflammatory environment and enhance the IVD matrix production. Removal of senescent cells, using senolytics drugs, could lead to improved therapeutic interventions and ultimately decrease pain and a provide a better quality of life of patients living with intervertebral disc degeneration and low back pain.
From Ying Ann Chiao of Oklahoma Medical Research Foundation: Mitochondrial dysfunction plays a central role in aging and cardiovascular disease. However, it was unclear whether improving mitochondrial function at late-life can rescue pre-existing age-related cardiac dysfunction, especially diastolic dysfunction. Here, we show that 8-week treatment with a mitochondrial-targeted peptide SS-31 (elamipretide) can substantially reverse pre-existing cardiac dysfunction in old mice. At molecular levels, late-life SS-31 treatment reduces mitochondrial ROS levels and normalizes age-related increases in mitochondrial proton leak and protein oxidative modifications. Late-life viral expression of mitochondrial-targeted catalase (mCAT) similarly improves diastolic function in old mice. SS-31 treatment cannot further improve cardiac function of old mCAT mice, implicating normalizing mitochondrial oxidative stress as an overlapping mechanism. Our results demonstrate that pre-existing cardiac aging phenotypes can be reversed by targeting mitochondrial dysfunction and support the therapeutic potentials of mitochondrial-targeted interventions in cardiac aging.