Mikhail ‘Misha’ Blagosklonny’s enduring legacy in geroscience: the hyperfunction theory and the therapeutic potential of rapamycin DOI Creative Commons

David Barzilai

Aging, Год журнала: 2025, Номер unknown

Опубликована: Янв. 12, 2025

The untimely passing of Dr. Mikhail "Misha" Blagosklonny has left a lasting void in geroscience and oncology. This review examines his profound contributions, focusing on pioneering the Hyperfunction Theory advocacy for rapamycin, an mTOR inhibitor, as therapeutic agent lifespan extension. Contrary to traditional damage-centric models, rejects damage accumulation primary driver aging. Instead, it redefines aging quasi-programmed process driven by persistent, excessive activity growth-promoting pathways beyond their developmental roles, leading age-related pathologies. We explore how Blagosklonny's insights predict rapamycin's ability decelerate modulating signaling, supported empirical evidence across multiple physiological systems, including immune, cardiovascular, cognitive, oncologic health. His forward-thinking approach, advocating cautious clinical use rapamycin suggesting personalized, preventive, combination therapy strategies, catalyzed interest translational geroscience. synthesizes legacy, presenting foundational pharmacological intervention with potential managing decline extending healthspan, underlines impact shifting research from theoretical frameworks actionable interventions. work remains enduring inspiration, paving way toward treating modifiable condition.

Язык: Английский

Epigenetic clocks and programmatic aging DOI Creative Commons
David Gems,

Roop Singh Virk,

João Pedro de Magalhães

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102546 - 102546

Опубликована: Окт. 16, 2024

The last decade has seen remarkable progress in the characterization of methylation clocks that can serve as indicators biological age humans and many other mammalian species. While processes aging underlie these have remained unclear, several clues pointed to a link developmental mechanisms. These include presence vicinity clock CpG sites genes specify development, including those Hox (homeobox) polycomb classes. Here we discuss how recent advances programmatic theories provide framework within which be understood part process aging. This includes such evolve, mechanisms cause aging, they give rise late-life disease. combination ideas from evolutionary biology, biogerontology biology open path new discipline, gerontology (devo-gero). Drawing on properties clocks, offer hypotheses exemplify devo-gero thinking. We suggest controls trade-off between earlier fidelity later plasticity. also propose existence an evolutionarily-conserved sequence spanning ontogenesis, adult development both constrains determines evolution

Язык: Английский

Процитировано

10

Biological constraint, evolutionary spandrels and antagonistic pleiotropy DOI Creative Commons
David Gems, Carina Kern

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102527 - 102527

Опубликована: Окт. 5, 2024

Язык: Английский

Процитировано

6

Mikhail ‘Misha’ Blagosklonny’s enduring legacy in geroscience: the hyperfunction theory and the therapeutic potential of rapamycin DOI Creative Commons

David Barzilai

Aging, Год журнала: 2025, Номер unknown

Опубликована: Янв. 12, 2025

The untimely passing of Dr. Mikhail "Misha" Blagosklonny has left a lasting void in geroscience and oncology. This review examines his profound contributions, focusing on pioneering the Hyperfunction Theory advocacy for rapamycin, an mTOR inhibitor, as therapeutic agent lifespan extension. Contrary to traditional damage-centric models, rejects damage accumulation primary driver aging. Instead, it redefines aging quasi-programmed process driven by persistent, excessive activity growth-promoting pathways beyond their developmental roles, leading age-related pathologies. We explore how Blagosklonny's insights predict rapamycin's ability decelerate modulating signaling, supported empirical evidence across multiple physiological systems, including immune, cardiovascular, cognitive, oncologic health. His forward-thinking approach, advocating cautious clinical use rapamycin suggesting personalized, preventive, combination therapy strategies, catalyzed interest translational geroscience. synthesizes legacy, presenting foundational pharmacological intervention with potential managing decline extending healthspan, underlines impact shifting research from theoretical frameworks actionable interventions. work remains enduring inspiration, paving way toward treating modifiable condition.

Язык: Английский

Процитировано

0