Aging: therapeutics for a healthy future
Section snippets
Aging – what are we attempting to treat?
Many consider aging as a purely chronological phenomenon; it is an immutable fact that we all get older. However, this is a simplification as individuals all age functionally in different ways and the concept of “biological aging” is more relevant than chronological aging (Khan et al., 2017). When we consider biological aging, we have a therapeutic target, not simply targeting getting old, rather treating physiological decline that is manifested by dysfunction and morbidity in late life. When
Issues involved in developing anti-aging therapies
A therapeutic that halts or prevents aging, putting off the onset of a debilitating disorder, could lead to a longer life. Extending life on the face of it is highly positive; the vast majority of the population looks forward to a long and fruitful life. However, if anti-aging therapies only increase lifespan without increasing healthspan it will just increase the population of diseased elderly, increasing healthcare spending and providing an undesirable, unsustainable, future for society. If
What may anti-aging therapeutics look like?
Is a golden bullet of a single drug to impact aging biology a realistic scenario? The diversity of age-related disorders, the multitude of potential endpoints, the complexities of genetic risk factors and environmental challenges accumulating over a lifetime all make a single therapeutic unlikely. However, if there are fundamental underlying mechanisms, such as cellular senescence or failure of proteostatic maintenance, or a natural mixture, such as plasma or a fraction of plasma able to
Funding and regulatory issues
Associated with the treatment of aging is a new set of interpretations of clinical success that go beyond purely scientific concepts. In particular, advancing a therapeutic for aging means that we have long timelines, yet to be validated outcome measures and a lack of clarity about the regulatory environment for such therapies. These challenges impact how aging therapeutics will be funded and considered. Nonetheless, there is an appetite by the broad community to achieve these goals and thus
Conclusions
We are at an exciting juncture where the realities of anti-aging therapies are upon us, and discussing how we can practically advance such approaches is a necessity. Even though a majority of research and therapeutic development focuses on individual domains such as neuroscience or behavior alone, thinking in the context of a systemic impact as we age provides wholly new opportunities, not only to tackle neurological disorders, but a spectrum of age-related ailments. The involvement of multiple
Acknowledgements
The authors thank Gabrielle LeBlanc (Leblanc Bioscience Consulting, Berkeley, CA) for help in writing the manuscript. This review is based in part on an open scientific satellite symposium titled “Aging: Therapeutics for a Healthy Future” held in conjunction with the 46th Annual Society for Neuroscience meeting in 2016, sponsored and organized by Charles River Laboratories. The meeting panelists included: Robert Hodgson (CNS Biology, Takeda, San Diego CA), Brian K. Kennedy (Yong Loo Lin School
References (57)
- et al.
Fasting or caloric restriction for healthy aging
Exp. Gerontol.
(2013) - et al.
Let-7 coordinately suppresses components of the amino acid sensing pathway to repress mtorc1 and induce autophagy
Cell Metab.
(2014) - et al.
Whole-genome sequencing of a healthy aging cohort
Cell
(2016) - et al.
Vascular biology of ageing-Implications in hypertension
J. Mol. Cell. Cardiol.
(2015) - et al.
Sarcopenia- the search for emerging biomarkers
Ageing Res. Rev.
(2015) - et al.
Geroscience: Linking aging to chronic disease
Cell
(2014) - et al.
Plasma-based strategies for therapeutic modulation of brain aging
Neurotherapeutics.
(2019) - et al.
models of ageing and their relevance to disease
Mech. Ageing and Dev
(2016) - et al.
The hallmarks of aging
Cell
(2013) - et al.
Key proteins and pathways that regulate lifespan
J. Biol. Chem.
(2017)
Therapeutic interventions for aging: the case of cellular senescence
Drug Discov. Today
Xbp1s in pomc neurons connects er stress with energy balance and glucose homeostasis
Cell Metab.
Fisetin is a senotherapeutic that extends health and lifespan
EBioMedicine.
Effect of aging on stem cells
World J. Exp. Med.
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Nature.
Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls
Diabetes Obes. Metab.
Metformin as a tool to target aging
Cell Metab.
Biochemical genetics pathways that modulate aging in multiple species
Cold Spring Harb. Perspect. Med.
From rapalogs to anti-aging formula
Oncotarget
Treating age-related diseases with somatic stem cells
Adv. Exp. Med. Biol.
Human umbilical cord plasma proteins revitalize hippocampal function in aged mice
Nature
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Nat. Med.
DNA methylation-based measures of biological age: meta-analysis predicting time to death
Aging
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Nat. Med.
Forward and reverse genetics approaches to uncover metabolic aging pathways in Caenorhaditis elegans
Biochim. Biophys. Acta
Aging: Progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes
Aging Cell
Effects of ageing and senescence on pancreatic β-cell function
Diabetes Obes. Metab.
DNA methylation age of human tissues and cell types
Genome Biol.
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