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Aging is emerging as a druggable target with growing interest from academia, industry and investors. New technologies such as artificial intelligence and advanced screening techniques, as well as a strong influence from the industry sector may lead to novel discoveries to treat age-related diseases. The present review summarizes presentations from the 7 th Annual Aging Research and Drug Discovery (ARDD) meeting, held online on the 1 st to 4 th of September 2020. The meeting covered topics related to new methodologies to study aging, knowledge about basic mechanisms of longevity, latest interventional strategies to target the aging process as well as discussions about the impact of aging research on society and economy. More than 2000 participants and 65 speakers joined the meeting and we already look forward to an even larger meeting next year. Please mark your calendars for the 8 th ARDD meeting that is scheduled for the 31 st of August to 3 rd of September, 2021, at Columbia University, USA.

Mitochondrial dysfunction is a hallmark of ageing, and mitochondrial maintenance may lead to increased healthspan. Emerging evidence suggests a crucial role for signalling from the nucleus to mitochondria (NM signalling) in regulating mitochondrial function and ageing. An important initiator of NM signalling is nuclear DNA damage, which accumulates with age and may contribute to the development of age-associated diseases. DNA damage-dependent NM signalling constitutes a network that includes nuclear sirtuins and controls genomic stability and mitochondrial integrity. Pharmacological modulation of NM signalling is a promising novel approach for the prevention and treatment of age-associated diseases., Competing Interests: statement The authors declare competing interests: see Web version for details.

China is encountering formidable healthcare challenges brought about by the problem of aging. By 2050, there will be 400 million Chinese citizens aged 65+, 150 million of whom will be 80+. The undesirable consequences of the one-child policy, rural-to-urban migration, and expansion of the population of 'empty nest' elders are eroding the traditional family care of the elders, further exacerbating the burden borne by the current public healthcare system. The challenges of geriatric care demand prompt attention by proposing strategies for improvement in several key areas. Major diseases of the elderly that need more attention include chronic non-communicable diseases and mental health disorders. We suggest the establishment of a home care-dominated geriatric care system, and a proactive role for researchers on aging in reforming geriatric care through policy dialogs. We propose ideas for preparation of the impending aging burden and the creation of a nurturing environment conducive to healthy aging in China., Competing Interests: No conflicts of interest., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span., (Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.)

These works uncovered a relatively comprehensive understanding of aging, and provided future perspectives for research on aging and aging interventions. Almost every cell in the body goes through the process of senescence, and the contribution of senescent cells to the body's unavoidable aging (we coined this "senescaging") cannot be ignored. Keywords: cellular senescence; aging; microenvironments; cellular communications; senescaging EN cellular senescence aging microenvironments cellular communications senescaging 1 3 3 04/14/22 20220411 NES 220411 Aging is expressed as a deterioration and frailty of various tissues, accompanied by dysregulation of the pathways essential for homeostasis, resilience, and maintenance ([1]; [6]; [7]). In recent years, many novel single-cell examination strategies have been constructed such as single-cell mass spectrometry ([13]), single-cell immunometabolic profiling ([2]), and single-cell-based immune cell research ([12]), allowing further exploration in the field of aging. [Extracted from the article]

Summary: Mitochondrial dysfunction is a common feature in neurodegeneration and aging. We identify mitochondrial dysfunction in xeroderma pigmentosum group A (XPA), a nucleotide excision DNA repair disorder with severe neurodegeneration, in silico and in vivo. XPA-deficient cells show defective mitophagy with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD+-SIRT1-PGC-1α axis triggered by hyperactivation of the DNA damage sensor PARP-1. This phenotype is rescued by PARP-1 inhibition or by supplementation with NAD+ precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration. Our findings reveal a nuclear-mitochondrial crosstalk that is critical for the maintenance of mitochondrial health. [ABSTRACT FROM AUTHOR]