The central problem the forum addressed is one that has long frustrated the longevity field: aging is a complex, multifactorial process, and without reliable molecular measures of biological age it is extraordinarily difficult to demonstrate that any candidate intervention actually slows it. Chronological age is a poor proxy, because individuals of the same age can differ dramatically in health status, disease risk and physiological reserve. Biomarkers of aging, measurable indicators that track biological aging more faithfully than the passage of time, therefore serve as the linchpin for translating laboratory discoveries into clinical trials. The forum’s organizers argued that the field has reached a point where such frameworks must be standardized, validated and deployed in human studies rather than remaining confined to retrospective cohort analyses.

Among the most prominent themes was the continued evolution of epigenetic clocks, the DNA methylation-based estimators of biological age pioneered by Steve Horvath of the University of California, Los Angeles, who presented at the meeting. Horvath and collaborators recently described pan-mammalian clock models in Nature Communications in 2024, extending methylation-based age estimation across species and tissues. These models exploit the fact that cytosine methylation patterns at specific genomic sites change predictably with age, allowing regression-based models trained on large reference datasets to predict chronological age from a tissue sample. Deviations between predicted and chronological age, the so-called age acceleration, have been associated in numerous studies with mortality risk and age-related disease. The forum discussions reportedly focused on refining these tools, including second-generation clocks trained on mortality and morbidity outcomes rather than chronological age alone, and on the interpretive caveats that arise when clocks are used to evaluate interventions.

That caveat is a serious one, and it featured prominently in the technical discussions. Work published in Cell Metabolism in 2023 by Poganik and colleagues demonstrated that biological age, as read out by multiple independent biomarkers, is not a fixed quantity but can fluctuate in response to stress, surgery and severe illness, and can recover afterward. This transient age acceleration and subsequent restoration implies that a single snapshot of a biomarker may mislead trial designers, and that repeated longitudinal sampling is essential to distinguish durable rejuvenation from short-term perturbation. Forum participants emphasized that intervention trials must therefore incorporate repeated measurements, appropriate control groups and pre-registered analytical pipelines to avoid spurious conclusions about whether a treatment has genuinely slowed aging.

A second major strand concerned organ-specific and proteomic aging clocks. Rather than estimating the age of the whole organism, these models estimate the biological age of individual organs or physiological systems, revealing that organs within a single person can age at markedly different rates. Recent work published in Cell Metabolism in 2025 by Goeminne and colleagues, and other proteomic studies discussed at the forum, showed that plasma protein signatures can be decomposed into organ-derived aging signals, opening the possibility of identifying which organ is failing fastest in a given individual and tailoring interventions accordingly. Related work by Yu and colleagues in Cell Metabolism in 2024 and by Bi and colleagues in 2025 extended this organ-centric view, and presentations by researchers including Jing-Dong J. Han of Peking University and Guangju Ji of the Henan Academy of Sciences covered multi-omic and computational approaches to constructing and validating such signatures in large human cohorts.

Inflammation emerged as a recurring mechanistic thread connecting many of the biomarkers under discussion. David Furman of Stanford University and the Buck Institute for Research on Aging presented work on immune-system aging, including the inflammatory signature known as iAge, described in Nature Aging in 2021, which uses a small set of circulating immune and chemokine markers to predict age-related decline and multimorbidity. Because chronic low-grade inflammation, sometimes termed inflammaging, contributes to a broad range of age-associated pathologies, immune-focused biomarkers offer a mechanistically interpretable complement to epigenetic and proteomic clocks. Furman’s discussion of iAge also illustrated the translational pathway the forum sought to highlight, since the signature has been developed into a commercial platform intended to support clinical decision-making and intervention monitoring.

Cellular senescence, the state of irreversible growth arrest that accumulates in aged tissues and secretes inflammatory and matrix-degrading factors, formed another pillar of the program. Presentations by Ning Jiang of West China Hospital and other speakers addressed the identification and quantification of senescent cell burden in accessible tissues and biofluids, a prerequisite for testing senolytic drugs, the compounds designed to selectively eliminate senescent cells. The field’s challenge, as framed at the forum, is that senescence markers such as p16INK4a, senescence-associated beta-galactosidase and the senescence-associated secretory phenotype are heterogeneous and context-dependent, so a validated circulating biomarker panel for senescent cell load remains an urgent unmet need for the senolytics pipeline.

The forum also looked beyond humans to comparative biology as a source of intervention targets. Vera Gorbunova and Andrei Seluanov of the University of Rochester presented their work on long-lived and cancer-resistant rodents, including naked mole-rats and blind mole-rats, whose unusual genome maintenance and tumor-suppression mechanisms were detailed in a 2025 Nature paper by Firsanov and colleagues. Comparative studies of this kind identify naturally evolved protective mechanisms, such as enhanced DNA repair, high-molecular-mass hyaluronan and distinctive interferon responses, that can in principle be mimicked pharmacologically. Complementing this, Vincenzo Sorrentino of the National University of Singapore and Lu Dong discussed mitochondrial and proteostatic determinants of tissue aging, including work on NAD metabolism and the nutraceutical trigonelline published in Nature Metabolism in 2024, which linked circulating trigonelline levels to muscle mitochondrial function and suggested a plausible route to combating sarcopenia.

Genome instability and the limits of rejuvenation were addressed by Jan Vijg of Albert Einstein College of Medicine, whose presentations considered somatic mutation accumulation as a fundamental driver of aging and the implications this holds for how much biological age reversal is realistically achievable. Ana Maria Cuervo of Albert Einstein College of Medicine discussed chaperone-mediated autophagy, the selective lysosomal degradation pathway that declines with age, and the therapeutic prospects of pharmacologically restoring it. Raul Mostoslavsky of Massachusetts General Hospital and Harvard Medical School covered chromatin and metabolic regulation of aging, while Susanna Rosi of Altos Labs presented work on cellular reprogramming and neural rejuvenation, an approach that resets epigenetic age in specific cell populations and has shown functional recovery in models of brain injury and neurodegeneration.

The report closes by looking forward: the organizers announced a 7th TimePie Longevity Forum for 2026, and the emerging directions summarized in the meeting report point toward standardized, multi-modal biomarker panels that combine epigenetic, proteomic, immune and imaging readouts, deployed in longitudinal human cohorts and intervention trials. The competing-interest disclosures accompanying the report, which include inventorship on epigenetic biomarker patents, company founder roles and advisory positions among several authors, underscore how quickly the field is moving from academic measurement toward commercial application. What the Shanghai meeting made clear is that the bottleneck in geroscience is no longer the identification of candidate targets in model organisms but the credible demonstration, in people, that a therapy has changed the trajectory of biological aging, and that this demonstration will stand or fall on the quality of the biomarkers used to measure it.

Subject of Research: Aging biomarker development and geroscience intervention discovery discussed at the 6th TimePie Longevity Forum in Shanghai

Article Title: Advancing aging biomarkers and intervention discovery at the TimePie Longevity Forum

Article References: Ying, K., Bie, J., Chen, G., Cuervo, A. M., Deng, H., Dong, L., Furman, D., Gorbunova, V., Han, J.-D. J., Horvath, S., Ji, G., Jiang, N., Mostoslavsky, R., Rosi, S., Seluanov, A., Sorrentino, V., Tang, Y., Vijg, J., & Yang, Q. (2026). Advancing aging biomarkers and intervention discovery at the TimePie Longevity Forum. Nature Aging. https://doi.org/10.1038/s43587-026-01226-8

Image Credits: AI Generated

DOI: 10.1038/s43587-026-01226-8

Keywords: aging biomarkers, epigenetic clocks, geroscience, longevity forum, cellular senescence, proteomic aging clocks, inflammaging, senolytics, chaperone-mediated autophagy, somatic mutations, comparative biology, NAD metabolism