LongeCityNews Last Updated: 14 April 2026 - 01:41 AM

A sizable body of evidence indicates that transposons contribute to degenerative aging. Transposons of various categories are DNA sequences that code for molecular machinery capable of writing copies of the original DNA into other locations in the genome. They are largely the remnants of ancient retroviral infections, altered and degraded over evolutionary time, while likely remaining an important mechanism of mutational change for future evolution. Transposons are suppressed in youth, the nuclear DNA sequences spooled and hidden from transcriptional machinery, but one of the noteworthy aspects of aging is a loss of epigenetic control over nuclear DNA structure and thus over gene expression. Stretches of DNA containing transposons unspool and become accessible to transcriptional machinery. Transposon expression produces molecules that are sufficiently virus-like for evolved defenses to react with inflammatory signaling, while the haphazard insertion of transposon sequences is a form of DNA damage, breaking genes.

Just like retroviruses, retrotransposons require reverse transcription to function. That part of the research and development community focused on HIV, human immunodeficiency virus, has spent decades developing ever better means of sabotaging reverse transcription. In today's open access paper, researchers report on their investigation of the effects of such antiretroviral drugs on measures of biological age. The researchers made use of data and samples originating from pharmacokinetic clinical studies of combinations of antiretroviral drugs in healthy volunteers. One combination of drugs did reduce measures of biological age, while the other did not. This suggests that there is indeed something interesting here, but that the fine details matter when it comes to the implementation of transposon suppression.

An FDA-Approved Tenofovir Alafenamide-Based Antiretroviral Therapy Reduces Biological Age in Healthy Adults: First Human Proof-of-Concept for Retrotransposon-Targeted Gerotherapeutics

Nearly half of the human genome (∼45%) is composed of transposable elements (TEs). Aging is accompanied by a progressive erosion of epigenetic silencing that permits the transcriptional reactivation of these TEs, particularly retrotransposons such as LINE-1 and endogenous retroviruses. In young somatic cells, these elements are maintained in a transcriptionally inert state by DNA methylation, heterochromatin, and KRAB-ZFP/KAP1 surveillance. However, with age the fidelity of these mechanisms declines, and retrotransposon-derived transcripts and cytoplasmic DNA accumulate. This age-dependent retroelement reactivation is now recognized as a proximal driver of biological aging hallmarks including a senescence-associated secretory phenotype (SASP) and age-related tissue dysfunction.

The dependence of retroelements on reverse transcription has made nucleoside reverse transcriptase inhibitors (NRTIs), which were developed and licensed for HIV treatment and prevention, attractive candidate gerotherapeutics. For instance, a retrospective analysis of longitudinal aging intervention studies identified antiretroviral therapy as one of the most consistent interventions associated with reductions across 16 epigenetic clocks. Early mechanistic work showed that multiple NRTIs including 3TC (lamivudine), tenofovir disoproxil fumarate (TDF), stavudine, and zidovudine can directly suppress human LINE-1 retrotransposition in cell-based reporter systems. Consistent with this, 3TC (lamivudine) blunted LINE-1 cDNA-triggered type I interferon signaling and components of the SASP in senescent human cells and reduced age-associated inflammatory signatures across multiple tissues in aged mice.

Here we evaluated DNA methylation-based measures of biological aging in healthy people without HIV (aged 18-50) using samples from two separate randomized, directly observed dosing pharmacokinetic studies of FDA-approved NRTI regimens containing emtricitabine / tenofovir-alafenamide (FTC/TAF; 200 mg/25 mg) or FTC / tenofovir-disoproxil fumarate (FTC/TDF; 200 mg/300 mg) for 12 weeks.

In the FTC/TAF study (N=36), epigenetic aging measures based on DNA methylation (DNAm) profiling decreased over follow-up, including DunedinPACE (-0.061) and PhenoAge (-6.33), with concordant reductions across additional systems-specific epigenetic clocks including those estimating brain aging. DNAm-based proxies of inflammatory biomarkers also declined, with significant reductions in epigenetic IL-6 (-0.058) and a trend toward reduced C-reactive protein (-0.231). In contrast, the FTC/TDF study (N=43) showed no significant changes across epigenetic clocks and proxies. These findings are consistent with TAF's more favorable cellular pharmacology compared with TDF and support gerotherapeutic effects of FTC/TAF.

Prospective placebo-controlled studies are warranted that integrate clinical pharmacology, direct transposable element readouts, and prespecified geroscience and DNA methylation-based aging endpoints.

In Aging Cell, researchers have described how one dermal protein is related to maintaining the populations of fast-cycling skin cells and preserving skin integrity.

Not all skin cells are the same

The outer layer of the skin (the epidermis) is naturally regenerated by two distinct populations of stem cells: slow-cycling and fast-cycling [1]. The former are distinguished by the expression of DLX1, while the latter express SLC1A3 [2]. However, with aging, the fast-cycling type begins to decline [3].

This decline occurs alongside several other markers of skin aging. The extracellular matrix (ECM), most known for maintaining tissue integrity and well-known to be damaged with aging, also has significant effects on the behavior of skin cells [4]. Integrins, which give signals to cells about the extracellular environment, decline with aging as well [5]. Further work has found that one particular extracellular matrix component, fibulin-7, is crucial to allowing the proliferation of fast-cycling skin cells [3].

This work focuses on a related protein, fibulin-5, which was also found to decrease with aging [6] and has been documented to directly interact with integrins [7]. This paper, then, set out to demonstrate that it may also be related to the loss of fast-cycling cells.

Mice without fibulin-5 age faster

The researchers created a strain of mice that do not express fibulin-5. Even when young, these mice had loose skin much like that of much older wild-type mice. Additionally, their coats were browner from their usual black, their hair was thinner, and they had less body weight. By 12 months of age, their skin was significantly thinner than that of wild-type mice.

At very young ages, these mice had similar proportions of interscale and scale areas that represent the homes of slow-cycling and fast-cycling skin cells. However, at 12 months, the scale areas were significantly diminished compared to those of wild-type mice, representing a decline in fast-cycling cells.

The modified mice also had significantly diminished amounts of many genes needed for proper skin maintenance, including genes related to replication, cellular adhesion, formation of the extracellular matrix, and one form of signaling. Inflammatory cytokines and a different signaling pathway were upregulated instead. These changes were found to have many aspects in common with ordinary aging.

There was also a significant decrease in the integrity of the ECM at the junction between the epidermal and dermal layers of skin. Like in naturally aged mice, two related  integrins and a crucial collagen were downregulated; however, unlike the naturally aged mice, the mice without fibrulin-5 had another integrin downregulated as well. The researchers found that the interaction between integrin β3 and the cellular adhesion molecule nectin-3 was diminished in both naturally aged wild-type mice and in the fibrulin-5 knockout mice.

Cells need to YAP at each other

The overall loss of fast-cycling skin cells was found to be related to the YAP intercellular signaling pathway. There was a decrease in YAP in the mice deficient in fibrulin-5, aged wild-type mice, and skin cells derived from human patients. Using verteporfin to inhibit YAP in wild-type mice significantly decreased their populations of fast-cycling skin cells, and using verteporfin on human skin cells decreased their expression of SLC1A3 as well. Directly exposing these cells to fibulin-5, on the other hand, promoted the expression of SLC1A3, signifying that this compound promotes a fast-cycling state.

The researchers, however, did not administer fibulin-5 to living animals, nor did they perform any experiments that increase YAP in mice. Such future work will determine if this is a potential path towards rebalancing these cellular populations and potentially treating this form of skin aging in people.

Literature

[1] Ghuwalewala, S., Lee, S. A., Jiang, K., Baidya, J., Chovatiya, G., Kaur, P., … & Tumbar, T. (2022). Binary organization of epidermal basal domains highlights robustness to environmental exposure. The EMBO journal, 41(18), EMBJ2021110488.

[2] Sada, A., Jacob, F., Leung, E., Wang, S., White, B. S., Shalloway, D., & Tumbar, T. (2016). Defining the cellular lineage hierarchy in the interfollicular epidermis of adult skin. Nature cell biology, 18(6), 619-631.

[3] Raja, E., Changarathil, G., Oinam, L., Tsunezumi, J., Ngo, Y. X., Ishii, R., … & Sada, A. (2022). The extracellular matrix fibulin 7 maintains epidermal stem cell heterogeneity during skin aging. The EMBO Reports, 23(12), EMBR202255478.

[4] Wang, Y., Kitahata, H., Kosumi, H., Watanabe, M., Fujimura, Y., Takashima, S., … & Natsuga, K. (2022). Collagen XVII deficiency alters epidermal patterning. Laboratory investigation, 102(6), 581-588.

[5] Giangreco, A., Goldie, S. J., Failla, V., Saintigny, G., & Watt, F. M. (2010). Human skin aging is associated with reduced expression of the stem cell markers β1 integrin and MCSP. Journal of Investigative Dermatology, 130(2), 604-608.

[6] Kadoya, K., Sasaki, T., Kostka, G., Timpl, R., Matsuzaki, K., Kumagai, N., … & Amano, S. (2005). Fibulin‐5 deposition in human skin: decrease with ageing and ultraviolet B exposure and increase in solar elastosis. British Journal of Dermatology, 153(3), 607-612.

[7] Budatha, M., Roshanravan, S., Zheng, Q., Weislander, C., Chapman, S. L., Davis, E. C., … & Yanagisawa, H. (2011). Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. The Journal of clinical investigation, 121(5), 2048-2059.

The Asia-Pacific Longevity Medicine Society (APLMS), in partnership with The Kitalys Institute, announced that the 2026 Asia-Pacific Healthy Longevity International Summit (APAC-LMIS) will be held in Hong Kong from October 1–4, 2026, at the Hopewell Hotel.

The Summit is expected to bring together more than 2,000 global leaders across longevity medicine, geroscience, pharmas, digital health, artificial intelligence, and regulatory science. As aging populations reshape healthcare systems and economic priorities worldwide, the event positions Hong Kong as a strategic hub for advancing innovation and collaboration in the rapidly expanding longevity economy.

Organized under the theme “From Vision to Action in Healthy Longevity,” the Summit will focus on accelerating the translation of scientific breakthroughs into scalable clinical practice and real-world health solutions.

Pre-summit programs (October 1–2) will include a curated series of high-impact activities, such as the Global Top 10 Longevity Breakthrough Awards, executive training for longevity clinic leaders, and expert-led sessions on regulatory frameworks and emerging technologies. The main Summit (October 3–4) will emphasize cross-sector collaboration, bringing together academia, healthcare providers, industry innovators, and policymakers to define next-generation standards, investment pathways, and delivery models in healthy longevity.

A central focus of the Summit will be the role of longevity clinics as the front line of clinical translation, alongside the integration of lifestyle medicine, digital health platforms, and AI-driven systems to enable earlier, more personalized interventions.

“The future of longevity medicine is no longer just about scientific discovery—it is about implementation at scale,” said the organizers. “This Summit is designed to connect research, clinical practice, regulation, and investment to accelerate real-world impact.”

With strong support from regional partners and growing international participation, the 2026 APAC-LMIS is expected to become a flagship global platform for advancing healthy longevity across the Asia-Pacific region and beyond.

Contact email: bd@apaclongevitysociety.org

About The Asia-Pacific Longevity Medicine Society (APLMS) www.apaclongevitysociety.org

The mission of APLMS is to promote the vision of “Live Longer, Live Healthier and Embrace the Best Lifestyle.”

The Asia-Pacific Longevity Medicine Society (APLMS) is a newly established non-profit professional organization registered in Hong Kong, China. Its founding member regions and countries include Mainland China, Hong Kong, Taiwan, Macau, Japan, South Korea, Singapore, Thailand, Australia and India.

APLMS is governed by a nine-member Executive Board, with each member representing one of the founding regions or countries. Dr. Tim Z. Shi, MD, PhD, Chief Representative of the GlobalMD Organization China Office, has been elected to serve as the Founding Chairman.

Additionally, APLMS has appointed twenty-one international advisory board members, representing global expertise across longevity medicine, geroscience, precision medicine, longevity technology, functional medicine, AI and digital health, clinical research and the pharmaceutical sector.

Key Focus Areas:

• Education and Advisory: Hosting conferences and creating educational content for scientists, industry leaders, longevity clinics, and the public;
• Collaboration: Building a network of researchers, entrepreneurs and investors dedicated to the longevity field;
• Coordination: Initiating and coordinating regional clinical trials and facilitating data sharing across member countries;
• Policy: Advocating for regulatory frameworks that support the advancement of longevity therapeutics.

Global Top 10 Longevity Breakthrough Awards:

https://longevityawards.org/

About The Kitalys Institute

Kitalys Institute (www.kitalys.org) is a 501©(3) tax-exempt not-for-profit organization dedicated to accelerating the translation of science into public health to prevent chronic diseases and extend healthy longevity for all.  Kitalys, and previously, its affiliate, Kinexum, a life sciences strategic advisory firm (www.kinexum.com), have been organizing the Targeting Healthy Longevity (previously Targeting Metabesity) conference, which since 2017 has convened leaders of NIH, FDA, Congress, the UK Parliament, geroscience and chronic disease research, industry and capital markets to identify obstacles and solutions to the emergence of the age of healthy longevity for all.  Over 200 conference sessions are posted on Kitalys’s YouTube channel at www.healthy-longevity.org. Kitalys has advised XPRIZE Healthspan and ARPA-H PROSPR on strategic regulatory matters, and proposed draft legislation, the THRIVE Act, that establishes an optional regulatory pathway, escalating tiers of evidence and incentives for drugs, devices and supplements that increase healthspan, while Kinexum represents a number of longevity biotech companies, including semi-finalists in XPRIZE Healthspan.

There are apparently a great many people who at least intermittently use psilocybin. Interestingly, regular dosing with psilocybin has been shown to modestly extend life in mice, but it is likely that only a subset of human users approach the frequency of dosing used in the mouse studies. Finding those humans is ever the challenge, particularly if one wants to study long-term effects on aging. Here, a researcher takes an initial stab at comparing the longevity of psilocybin users with non-users based on publicly available information, but the sample size is so small that it isn't surprising to see a lack of useful results. The study is more interesting as a way to provoke (a) awareness of the evidence for psilocybin to interact with mechanisms of aging, and (b) some thought on what sort of study design would be both practical and useful.

Researchers have reported that psilocybin promotes resilience and extends lifespan in aged mice. This work garnered considerable media attention, with claims that psychedelics might also extend human lifespan. Psychedelics influence longevity-related pathways in rodents such as glucocorticoid receptor signaling and mitochondrial stress tolerance. In light of these findings and in search of some evidence that psychedelics can indeed extend human lifespan, we examined historical mortality patterns of psychedelic personalities (researchers and advocates who had documented, mostly self-claimed, psychedelic use) and compared this group to biomedical researchers (cancer and aging).

Using publicly available records, we identified individuals who died between 2010 and 2025: (i) psychedelic personalities with documented personal use (n = 11), (ii) cancer researchers (n = 12), and (iii) aging researchers (n = 5). Deaths before age 60 were excluded. Conditional life expectancy at age 40 for their birth cohorts (≈73-76 years, US/UK data) was used as a baseline. All three groups lived well beyond population averages, consistent with the survival advantage of highly educated professionals. Crucially, the psychedelic personalities did not outlive their biomedical peers.

Thus, while researchers have provided compelling mechanistic data in mice, translation to humans requires dose-specific and longitudinal studies to identify whether psychedelics such as psilocybin do indeed have some role in extending lifespan.

Link: https://doi.org/10.1038/s41514-026-00380-y