"Living young appears to be a strategy of living long."
BUFFALO, NY — September 24, 2026 — A new review was published in Volume 18 of Aging on September 8, 2026, titled " How to live for centuries: common denominators of organisms with exceptional longevity ."
The review examines what some of the world's longest-lived organisms may reveal about the biology of exceptional longevity.
The review was led by first author Stefania E. Kapsetaki from the Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH), in Heraklion, Crete, Greece . Corresponding author Nektarios Tavernarakis is affiliated with the same institute and with the Division of Basic Sciences, School of Medicine, University of Crete .
Kapsetaki and Tavernarakis surveyed molecular and cellular evidence from 101 multicellular species with maximum lifespans of at least 250 years, including 90 plants and 11 animals. Some reach only slightly beyond 250 years, while others may persist for thousands or even tens of thousands of years. The freshwater planarian Schmidtea mediterranea and the jellyfish Turritopsis dohrnii are even considered potentially immortal.
Rather than looking only at why certain species live longer than others, the authors compared two dimensions of longevity: variation within exceptionally long-lived species and variation between long- and shorter-lived species. Their analysis covered genetic, genomic, transcriptomic, proteomic and metabolomic findings, as well as telomere maintenance, stress resistance, regeneration and tumorigenesis.
Across species, several recurring biological features emerged. Compared with shorter-lived species, extremely long-lived organisms are often characterized by better DNA maintenance, resistance to cellular and environmental stress, regenerative capacity, preservation of stem-cell populations and mechanisms that may suppress cancer development. Comparative genomic studies have also identified longevity-associated pathways involved in apoptosis, protein homeostasis, oxidative-stress resistance and responses to environmental damage.
Regeneration appears particularly important in some of the most unusual long-lived organisms. Hydra can regularly replace its cells, while Turritopsis dohrnii can reverse to an earlier developmental stage. Planarian stem cells, known as neoblasts, can generate multiple cell types and support extraordinary regenerative capacity. Long-lived plants such as Pinus sylvestris and Ginkgo biloba also appear to preserve cell pluripotency better during aging than shorter-lived plants.
However, the review also challenges the idea that one familiar aging mechanism can explain exceptional longevity. Telomere length, telomerase activity, metabolic rate and antioxidant activity do not consistently account for lifespan differences among individuals within exceptionally long-lived species. For example, telomere characteristics vary by species and even by tissue, suggesting that extreme longevity arises from multiple interacting biological strategies rather than a universal molecular switch.
Cancer resistance may be another component. Despite long lifespans and extensive cell renewal, tumors appear relatively uncommon in several exceptionally long-lived species. Planarians, for example, combine remarkable regenerative capacity with DNA-repair mechanisms and conserved regulators of cell division. The authors suggest that the anticancer adaptations of long-lived organisms deserve further investigation, while emphasizing that available evidence remains incomplete.
Importantly, the review identifies similarities between mechanisms associated with lifespan variation within species and those distinguishing longer-lived species from shorter-lived ones.
"Both types of variation include mechanisms related to DNA maintenance, stemness, and stress resistance-related pathways."
These mechanisms are also characteristic of early developmental stages and germ cells, leading the authors to summarize the pattern with the observation that "Living young appears to be a strategy of living long."
The authors also emphasize that longevity cannot be separated from the environment. Temperature, ecological pressures and other environmental conditions may interact with molecular pathways over evolutionary timescales. These relationships differ substantially among species, making it difficult to generalize a particular environmental condition as longevity-promoting.
Although the biology of exceptionally long-lived organisms could eventually reveal targets relevant to human health and aging, the review does not establish that their longevity mechanisms can be directly transferred to humans. Instead, these species provide comparative biological models for identifying pathways that warrant further mechanistic and translational investigation.
Major knowledge gaps also remain. Many exceptionally long-lived species have received little molecular study, available investigations use different methods and tissues, and laboratory conditions may not reflect life in the wild. The field also lacks comprehensive cross-species healthspan data comparable to existing lifespan databases. Larger studies using standardized methods and incorporating environmental information will therefore be needed to distinguish causal longevity mechanisms from associations.
Overall, the review suggests that living for centuries is unlikely to depend on a single gene or pathway. Instead, exceptional longevity appears to involve overlapping strategies for maintaining DNA, preserving regenerative capacity and stemness, resisting stress and limiting cancer development. Understanding how these mechanisms operate across the tree of life may provide new directions for studying healthy aging and longevity.
Paper DOI: https://doi.org/10.18632/aging.206419
