LongeCityNews Last Updated: 03 January 2026 - 02:58 AM

That genetic variation appears to determine little of the variation in life expectancy for the vast majority of people is perhaps the most useful information yet to emerge from the creation of very large databases of genetic and health information, such as the UK Biobank. That this is the case doesn't rule out the existence of rare beneficial mutations with relatively large effects on life expectancy, however. See, for example, the PAI1 loss of function mutants who appear to live seven years longer than near relatives - though one should be wary of small sample sizes when it comes to determining the size of the effect in these circumstances.

In today's open access paper, researchers report on their identification of a rare mutation in cGAS, an important determinant of age-related chronic inflammation. When nuclear DNA or mitochondrial DNA is mislocalized in the cell as a result of age-related damage and dysfunction, cGAS is a part of the maladaptive process by which the STING pathway is triggered to produce an inflammatory response. This pathway evolved to defend against infectious pathogens, so one can't just turn off cGAS-STING signaling because it is essential to normal immune function and health. Too much of it is a bad thing, however, and important in degenerative aging. This newly discovered mutation appears to split the difference, resulting in greater longevity without evidently impaired function.

One might compare this discovery with recent work in the comparative biology of aging, where cGAS and STING are shown to be less inflammatory in response to the molecular damage of aging in long-lived species. For example, researchers have engineered mice to express the less inflammatory naked mole-rat cGAS, and this has the outcome of reducing age-related inflammation to slow degenerative aging. Similarly, another research group engineered mice to expresss the STING gene from bats, which also produced a beneficial reduction in age-related inflammation.

Rare longevity-associated variants, including a reduced-function mutation in cGAS, identified in multigenerational long-lived families

Life expectancy has steadily increased in the last two centuries, while healthspan has been lagging behind. Survival into extreme ages strongly clusters within families which often exhibit a delayed onset of (multi)morbidity, yet the underlying protective genetic mechanisms are still largely undefined. We performed affected sib-pair linkage analysis in 212 sibships enriched for ancestral longevity and identified four genomic regions at 1q21.1, 6p24.3, 6q14.3, and 19p13.3. Within these regions, we prioritized 12 rare protein-altering variants in seven candidate genes (NUP210L, SLC27A3, CD1A, CGAS, IBTK, RARS2, and SH2D3A) located in longevity-associated loci.

Notably, a missense variant in CGAS (rs200818241), was present in two sibships. Using human- and mouse-based cell models, we showed that rs200818241 reduced protein stability and attenuated activation of the canonical cGAS-STING pathway in a cell-type specific manner. This dampened signalling mitigated inflammation and delayed cellular senescence, mechanisms that may contribute to the survival advantage of CGAS variant carriers. Our findings indicate novel rare variants and candidate genes linked to familial longevity and highlight the cGAS-STING pathway as a potential contributor to the protective mechanisms underlying human longevity.

Longevity Investors announces the upcoming Longevity Investors Lunch 2026, an exclusive, application-only gathering designed specifically for investors seeking exposure to the most compelling opportunities emerging at the intersection of longevity science, technology, and capital. Held during the World Economic Forum in Davos, the event convenes a highly curated group of global investors alongside select longevity scientists, researchers, and industry leaders shaping the future of health and aging.

Since its launch in 2022, the Longevity Investors Lunch has established itself as a trusted platform – one that bridges capital allocators with frontier science, applied longevity technologies, and academically-driven innovation moving toward commercialization. The event is purpose-built to translate scientific progress into investable insight, enabling informed capital deployment.

Inside the Longevity Investors Lunch in Davos — curated discussions bringing together investors, scientists, and industry leaders in an intimate setting.

The 2026 program will feature expert-led panels, focused insights, and curated networking sessions designed to foster meaningful dialogue and long-term collaboration between investors and the scientific community. Discussions will focus on areas including translational longevity science, computational biology, precision medicine, AI-enabled healthcare, and scalable interventions targeting aging and age-related disease. All discussions are shaped through an investor lens rather than purely academic exploration.

Announced Speakers for LIL 2026

Prof. Evelyne Yehudit Bischof, MD, PhD, MPH

Director, Sheba Longevity Center

Internationally recognized physician-scientist advancing translational longevity medicine, clinical innovation, and evidence-based health optimization.

Jordan Shlain, MD

Founder & Chairman, Private Medical

Physician, entrepreneur, and healthcare innovator known for advancing prevention-first medical care and long-term health strategy.

Dr. Liv Kraemer, MD, PhD

Founder, Dr. Liv Kraemer Skin Longevity Clinic

Dermatologist and longevity researcher specializing in skin biology, preventive dermatology, and personalized aesthetic-health integration.

Peter Fedichev

CEO, GERO.ai

Computational biophysicist and AI pioneer focused on aging biomarkers, systemic resilience, and data-driven longevity therapeutics.

Dr. Andrea Gartenbach, MD

Longevity Physician, Axmann/Gartenbach

Internal medicine specialist and longevity expert focusing on cardiometabolic prevention, functional and hormone-based therapies, and personalized performance-driven health optimization.

Dr. Neven Pičuljan, PhD

Co-Founder, Aion Longevity

AI engineer and technology entrepreneur applying machine learning to integrate wearable data, lab results, and longitudinal wellbeing signals—advancing personalized, data-driven longevity analytics and precision health insights.

“We are proud to host the fifth edition of our Longevity Investors Lunch in January 2026 in Davos as a side-event during the World Economic Forum. Our vision and ambition is still the same: to bring more money into the emerging longevity industry by attracting investors in Davos who support research and startups in the industry.“ says Marc P. Bernegger, Co-Founder and Host of Longevity Investors.

“Longevity is developing at an extraordinary pace, yet many still wonder where the meaningful inflection points lie. LIL 2026 in Davos gives us the opportunity to filter out the noise, examine what the science really tells us, and connect investors with the innovators building solutions that can genuinely enhance healthspan.” says Dr. Tobias Reichmuth, Co-Founder and Host, Longevity Investors

Longevity Investors Co-Founders Marc P. Bernegger and Dr. Tobias Reichmuth, CEO Lucy Kupcova, and LIL 2025 speaker Dr. Deepak Chopra at the Longevity Investors Lunch in Davos.

LIL 2026 builds on a longstanding tradition of convening leaders who shape the future of healthspan, medicine, and scientific progress. As longevity science accelerates, the gathering offers an essential platform for investors and innovators to align on the breakthroughs, trends, and foundational work driving the next wave of global health transformation.

That dialogue continues with the seventh edition of the Longevity Investors Conference, taking place September 14–17, 2026, in Gstaad, Switzerland. Hosted in a private, invitation-only setting at a 5-star luxury hotel, the Longevity Investors Conference is the world’s most private investor conference dedicated to longevity, bringing together key opinion leaders, institutional and private investors, family offices, and funds to explore the scientific and investment foundations of human healthspan extension.

Together, the Longevity Investors Lunch and the Longevity Investors Conference reflect a shared conviction: as advances in biotechnology, medicine, and data-driven science accelerate, longevity is emerging as one of the defining investment opportunities of the decades ahead—and requires informed capital, rigorous dialogue, and long-term perspective.

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Histones are structures in the cell nucleus that act as spools. Regions of nuclear DNA are compacted into a protected, inactive form when spooled around histones. The modification of histones by the addition and removal of chemical decorations are an important part of determining the winding and unwinding of DNA, and thus which gene sequences are exposed to translational machinery and can be expressed at any given time. One sizable component of aging is that this highly complex regulation of DNA structure changes, altering gene expression in undesirable ways.

Researchers here take initial steps towards mapping the effects on aging of succinylation of histones, the addition of a succinyl group. Their initial data suggests that more succinylation is a good thing, in that it correlates with greater longevity and a slower pace of aging. Providing mice with a diet supplemented with succinic acid to provoke greater histone succinylation produces modest benefits. That more succinylation is beneficial in this way is an unexpectedly direct outcome for something as complex as regulation of histone function, but the data is the data.

Histone post-translational modifications (PTMs) are critical regulators of chromatin structure and gene expression, with broad implications for development, metabolism, and aging. While canonical modifications such as methylation and acetylation are well characterized, the role of histone succinylation remains poorly understood.

Here, we investigated histone succinylation in the context of aging and exceptional longevity. Using mass spectrometry-based proteomics, we quantified histone succinylation in B-cells from four groups: young individuals, older individuals without parental longevity (OPUS), long-lived individuals, and offspring of long-lived individuals (OPEL). We found that histone succinylation was significantly elevated in the OPEL group compared to both young and OPUS cohorts. Nuclear proteomics further revealed enrichment of succinylated proteins in OPEL samples, supporting a role for succinylation in chromatin organization.

To test whether succinate availability impacts healthspan, we supplemented middle-aged mice with succinic acid. While body weight, frailty index, and cognition were unaffected, succinic acid improved motor coordination and muscle strength. Together, our findings provide preliminary evidence that enhanced histone succinylation may serve as a protective epigenetic mechanism in individuals predisposed to exceptional longevity, and that succinate supplementation can selectively improve aspects of physical performance during aging.

Link: https://doi.org/10.1111/acel.70346

Researchers here discuss the application of lipid nanoparticle delivery of messenger RNA as a basis for the development of cancer vaccines. As is the case for vaccines against infectious disease, there are many different ways to provoke an immune response to cancer-specific antigens. Use of messenger RNA to express the desired antigen is the most recent of these technologies. A great of effort has gone into the development of cancer vaccines over the years, and thus it seems likely that a wide range of messenger RNA cancer vaccines will be developed. As yet, however, little of this past effort has resulted in regulatory approval of cancer vaccines and use in the clinic. That low success rate may or may not change with the introduction of messenger RNA as an approach, time will tell.

The landscape of cancer immunotherapy has been redefined by mRNA vaccines as rapid clinically viable strategies that help induce potent, tumor-specific immune responses. This review highlights the current advances in mRNA engineering and antigen design to establish an integrated immunological framework for cancer vaccine development.

Achieving durable clinical benefit requires more than antigen expression. Effective vaccines need precise epitope selection, optimized delivery systems, and rigorous immune monitoring. The field is shifting from merely inducing immune responses to focusing more on the biochemistry and molecular design principles that combine magnitude, polyfunctionality, and longevity to overcome tumor-induced immune suppression.

We examine an integrated immunological framework for mRNA cancer vaccine development, examining how rational molecular engineering of vaccine components, from nucleoside modifications and codon optimization to untranslated regions and linker sequences, shapes immunogenicity and therapeutic efficacy. Future directions will depend on balancing combinatorial strategies combining vaccination with immune checkpoint inhibitors and adoptive cell therapies.

Link: https://doi.org/10.3390/vaccines13121222